Immunology Letters[JOURNAL]
Sun
200 papers
LCK at the crossroad of immunodeficiency and autoimmunity: Mechanisms and therapeutic opportunities.
Woessner NM, Keller B, Minguet S
Immunol Lett · 2026 Jun · PMID 41482192 · Publisher ↗
The lymphocyte-specific protein tyrosine kinase (LCK) is the principal initiator of T cell receptor (TCR) signaling and a critical regulator of T-cell development, activation, and immune tolerance. Its critical expressio...
The lymphocyte-specific protein tyrosine kinase (LCK) is the principal initiator of T cell receptor (TCR) signaling and a critical regulator of T-cell development, activation, and immune tolerance. Its critical expression in T cells positions LCK as both a molecular gatekeeper of adaptive immunity and an attractive therapeutic target. Loss-of-function mutations in LCK result in combined immunodeficiency with profound defects in T-cell differentiation and signaling, whereas hypomorphic variants with residual activity can promote immune dysregulation and autoimmunity. Conversely, aberrant LCK activation is associated with autoimmunity and chronic inflammation, including type 1 diabetes, psoriasis, rheumatoid arthritis, asthma, multiple sclerosis, and graft-versus-host disease. Here, we review the structural and regulatory mechanisms of LCK, its dysfunction in immunodeficiency and autoimmunity, and the current landscape of therapeutic strategies. While first-generation inhibitors targeting the ATP-binding site have shown efficacy in preclinical models, their lack of selectivity highlights the need for innovative approaches directed at non-catalytic domains of LCK. By linking mechanistic understanding with clinical relevance, we position LCK as a precision regulatory node with the potential to transform therapeutic strategies for T cell-driven immune disorders.
Design and application of a multi-epitope ACE2 antigen for detection of autoantibodies in post-COVID-19 diagnosed type 1 diabetes.
Marzban M, Ahmadi N, Sotoodehnejadnematalahi F … +1 more , Gholami A
Immunol Lett · 2026 Jun · PMID 41478466 · Publisher ↗
BACKGROUND: Type 1 diabetes mellitus (T1DM) is an autoimmune condition involving pancreatic β-cell destruction. Recent publications associate SARS-CoV-2 infection with autoimmune activation and the development of de novo...
BACKGROUND: Type 1 diabetes mellitus (T1DM) is an autoimmune condition involving pancreatic β-cell destruction. Recent publications associate SARS-CoV-2 infection with autoimmune activation and the development of de novo Type 1 Diabetes Mellitus (T1DM), possibly via molecular mimicry, inflammation, and direct β-cell damage. The angiotensin-converting enzyme 2 (ACE2) receptor, exploited by SARS-CoV-2 for cellular entry, is present in pancreatic islets and may be susceptible to autoantibody attack. This study was done to assess anti-ACE2 autoantibody titers in newly diagnosed patients with T1DM post-COVID-19 infection. METHODS: Blood samples were collected from thirty-five patients with new-onset T1DM post-COVID-19 and thirty healthy controls who recovered from COVID-19. Bioinformatic epitope prediction software was used to construct an eleven-epitope multi-epitope antigen of ACE2. The recombinant was cloned into BL21 E. coli via pET-32a+ vector, expressed, purified by affinity chromatography, and verified by Western blotting. Indirect ELISA was established to measure anti-ACE2 antibodies, and the Mann-Whitney test was applied for statistical comparison. RESULTS: The designed multi-epitope vaccine had significant structural stability and effective expression. ELISA results demonstrated significantly higher anti-ACE2 autoantibody levels in T1DM patients compared with the control group (p = 0.01). CONCLUSION: The results are consistent with a potential association between SARS-CoV-2 infection and the onset of T1DM by autoimmune responses against ACE2. Very high levels of anti-ACE2 antibodies may cause β-cell dysfunction and insulin deficiency. More longitudinal studies are required to establish causality and investigate anti-ACE2 as a prospective biomarker for post-COVID autoimmune diabetes.
TNFAIP8 targets ATG3 to regulate autophagy and participate in the molecular mechanism of ankylosing spondylitis.
Zhao Y, Ni M, Zhao H … +6 more , Ren Y, Li Z, Wu H, Xu L, Li G, Pan F
Immunol Lett · 2026 Apr · PMID 41422849 · Publisher ↗
Ankylosing spondylitis (AS) is an immune-mediated inflammatory joint disease. This study aims to explore the molecular mechanism by which tumor necrosis factor alpha-induced protein 8 (TNFAIP8) regulates autophagy in AS....
Ankylosing spondylitis (AS) is an immune-mediated inflammatory joint disease. This study aims to explore the molecular mechanism by which tumor necrosis factor alpha-induced protein 8 (TNFAIP8) regulates autophagy in AS. We collected 10 mL of peripheral venous blood from 48 patients with AS and 48 healthy controls, along with epidemiological data. The levels of inflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA). Then, CD3+ T lymphocytes were isolated via magnetic bead sorting, and the transcriptional levels of TNFAIP8 and autophagy-related genes (ATG3, ATG5, ATG7, ATG12, Beclin1, and LC3B) were determined by real-time quantitative PCR (qRT-PCR). Using small interfering RNA (siRNA) technology, we knocked down TNFAIP8 expression in Jurkat T cells. Next, qRT-PCR and Western blot (WB) were used to detect the mRNA and protein levels of TNFAIP8 as well as the autophagy markers p53, TFEB, ATG3, p62, and LC3. Co-immunoprecipitation (Co-IP) assays confirmed the interaction between TNFAIP8 and ATG3. In T cells from AS patients, TNFAIP8 and ATG3 levels are down-regulated and positively correlated (r = 0.350, P = 0.015). Further experiments demonstrated that si-TNFAIP8 reduced the mRNA and protein levels of ATG3. Co-IP verified TNFAIP8 interacts with ATG3.TNFAIP8 may regulate AS autophagy by targeting ATG3.
Compartment-specific activation of kinin B1 and B2 receptors drives the production of vasoactive and inflammatory mediators during SARS-CoV-2 infection.
de Lara JD, Vidal T, de Souza JB … +20 more , Kodavara E, Decker ER, Grotto FS, Bortoluzzi LD, Santini Dos Santos AP, Brusco I, de Oliveira SM, Viero FT, Glaser T, Wilot LC, Bernasconi TLG, Weber AAP, Librelotto DRN, Silveira MD, Sperotto NDM, Ulrich H, Basso LA, Bizarro CV, Mello CF, Pillat MM
Immunol Lett · 2026 Jun · PMID 41422848 · Publisher ↗
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) disrupts multiple host regulatory systems, including the kallikrein-kinin system (KKS), which plays a central role in vascular homeostasis and inflammation. Fo...
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) disrupts multiple host regulatory systems, including the kallikrein-kinin system (KKS), which plays a central role in vascular homeostasis and inflammation. Following viral entry, angiotensin-converting enzyme 2 (ACE2) is internalized and inactivated, impairing the degradation of des-Arg⁹-bradykinin (DABK), a selective agonist of the inducible kinin B1 receptor (B1R), while inflammatory feedback mechanisms may further elevate bradykinin (BK), the kinin B2 receptor (B2R) agonist. It has been postulated that the kinin storm observed in COVID-19 patients may lead to pulmonary angioedema, promote the exacerbated production of pro-inflammatory cytokines, and be related to disease progression, permanent sequelae, and death. However, it remains unknown whether in vitro SARS-CoV-2 infection triggers alterations in the KKS and its downstream inflammatory and vasoactive mediators. Here, we investigated how SARS-CoV-2 infection modulates kinin signaling and its downstream inflammatory and vasoactive mediators in Vero E6 and human endothelial (HUVEC) cells. SARS-CoV-2 infection increased BK levels and markedly upregulated B1R gene expression in Vero E6 cells (up to 20-fold), while B2R expression remained unchanged. Both BK and DABK reduced ACE2 expression in Vero E6 cells, an effect most likely mediated by DABK-B1R signaling due to the minimal expression of B2R in this cell line. Viral infection induced robust production of nitric oxide (NO) and interleukin-6 (IL-6) in Vero E6 cells, and supernatants from infected cells triggered similar responses in HUVECs. Pharmacological blockade of B1R with R-715 selectively prevented SARS-CoV-2-induced NO production in Vero E6 cells, whereas IL-6 induction occurred through B1R-independent mechanisms. In contrast, in endothelial HUVEC cells exposed to serum from patients with severe COVID-19, B2R antagonism with HOE-140 prevented both NO and IL-6 production, suggesting a key role for B2R in both vascular cytokine amplification and vasoactive mediator production. Our findings reveal a compartment-specific and complementary activation of B1R and B2R during SARS-CoV-2 infection, establishing the KKS as a key mediator of endothelial alterations and inflammatory amplification in COVID-19 and positioning B1R and B2R as therapeutic targets.
Potential link between COVID-19 infection/vaccination and the onsets of TAFRO syndrome and idiopathic multicentric castleman disease.
Umeda M, Mohamed L, Umetsu A … +7 more , Otsuka M, Endo Y, Shimizu T, Fukui S, Sumiyoshi R, Koga T, Kawakami A
Immunol Lett · 2026 Apr · PMID 41365367 · Publisher ↗
COVID-19 infection and vaccination have been reported as potential triggers for various autoimmune diseases, including TAFRO syndrome and idiopathic multicentric Castleman disease (iMCD). We investigated the incidence of...
COVID-19 infection and vaccination have been reported as potential triggers for various autoimmune diseases, including TAFRO syndrome and idiopathic multicentric Castleman disease (iMCD). We investigated the incidence of TAFRO syndrome and that of iMCD in the patients admitted to Nagasaki University Hospital over a 10-year period from November 2014 to October 2024. The primary endpoint was the incidences of TAFRO syndrome/iMCD before and after the COVID-19 pandemic. The secondary endpoint was the impact of COVID-19 vaccination ≤4 weeks of disease onset on the patients' prognoses. Our analyses revealed that in the 5 years and 5 month-period before the pandemic, there were seven cases of TAFRO syndrome/iMCD (1.3 cases/year), while in the 4 years and 7 month-period following the pandemic's onset, 18 cases were identified (3.9 cases/year). Specifically, for iMCD-TAFRO and TAFRO without iMCD, the incidence rose from two cases (0.4 cases/year) pre-pandemic to 11 cases (2.4 cases/year) post-pandemic, representing a marked increase. Among the 13 cases of iMCD-TAFRO and TAFRO without iMCD observed, four patients developed symptoms within 4 weeks of receiving the COVID-19 vaccine, and all required ICU admission. Conversely, among the nine patients without a recent vaccination history, only two required ICU care (p = 0.02). Although potential confounders which could influence the diagnosis (e.g., increased awareness of the disease) were not controlled for, our findings suggest a possible link between COVID-19 infection or vaccination and the onsets of TAFRO syndrome and iMCD. COVID-19 vaccination is a crucial public health strategy to reduce COVID-19-related death and disability, but TAFRO syndrome that develops post-vaccination may progress to severe illness requiring ICU care, highlighting the need for careful monitoring.
Lenvatinib-resistant liver cancer-derived HSP90α-containing extracellular vesicles enhance drug resistance via macrophage CXCL8 secretion.
Xu XW, Zhang Y, Zhao CW … +7 more , Wu H, Zhang MT, Ma YT, Yu Y, Zheng L, Gu F, Chen YQ
Immunol Lett · 2026 Apr · PMID 41349809 · Publisher ↗
The acquisition of lenvatinib resistance has a significant detrimental impact on the clinical efficacy of patients with hepatocellular carcinoma (HCC). Extracellular vesicles (EVs), which act as key mediators of intercel...
The acquisition of lenvatinib resistance has a significant detrimental impact on the clinical efficacy of patients with hepatocellular carcinoma (HCC). Extracellular vesicles (EVs), which act as key mediators of intercellular communication, are implicated in tumor progression and immune evasion. The aim of this research was to investigate whether EVs derived from lenvatinib-resistant HCC cells regulate tumor-associated macrophages and contribute to drug resistance in HCC. The results showed that lenvatinib-resistant HCC cell-derived EVs could upregulate the ERK pathway in macrophages, leading to the secretion of C-X-C motif chemokine ligand 8 (CXCL8), which, in turn, promoted HCC cells resistant to lenvatinib. Mechanistically, lenvatinib-resistant HCC cell-derived EVs regulate the Toll Like Receptor 2 (TLR2)-ERK pathway in macrophages through heat shock protein 90 alpha (HSP90α), thereby promoting the secretion of CXCL8, and activating STAT3 phosphorylation, which in turn upregulates the expression of Programmed Cell Death Ligand 1 (PD-L1). Subsequently, elevated levels of CXCL8 stimulated the CXCL8 receptor CXC chemokine receptor 1/2 (CXCR1/2) in HCC cells, inhibited lenvatinib-induced apoptosis, and increased the expression of P-glycoprotein (P-gp) and Vimentin, thereby promoting epithelial-mesenchymal transition (EMT) and drug resistance in liver cancer. Conversely, the inhibition of CXCR1/2 abolished its inhibitory effect on lenvatinib-induced apoptosis, and resulted in the downregulation of P-gp and Vimentin. In conclusion, our study demonstrated that EVs containing HSP90α, derived from lenvatinib-resistant liver cancer cells, can promote EMT and drug resistance in HCC cells by stimulating CXCL8 secretion from macrophages. This finding may provide new insights and strategies to overcome lenvatinib resistance in the future.
Interaction between IL-23/Th17 immune inflammatory axis and intestinal flora in gastric mucosal atrophy caused by Helicobacter pylori infection in the elderly.
Shen H, Zhu S, Ren L … +4 more , Chen F, Qian C, Hu X, Chen G
Immunol Lett · 2026 Apr · PMID 41297640 · Publisher ↗
OBJECTIVE: To explore the interactive effects of the interleukin-23 (IL-23)/Th17 immune-inflammatory axis and gut microbiota in gastric mucosal atrophy among elderly patients with Helicobacter pylori (HP) infection. METH...
OBJECTIVE: To explore the interactive effects of the interleukin-23 (IL-23)/Th17 immune-inflammatory axis and gut microbiota in gastric mucosal atrophy among elderly patients with Helicobacter pylori (HP) infection. METHODS: A total of 210 elderly patients with HP infection from Lishui Second People's Hospital between January 2023 and June 2024 were selected as the study group, and 210 healthy volunteers during the same period served as the control group. The IL-23/Th17 immune-inflammatory axis factors [IL-23, interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-2 (IL-2)], and gut microbiota were compared between the study and control groups. The study group was further divided into an atrophy subgroup (101 cases) and a non-atrophy subgroup (109 cases) based on the presence of gastric mucosal atrophy. Clinical data, IL-23/Th17 immune-inflammatory axis factors, and gut microbiota characteristics were compared between the two subgroups. Logistic regression analysis was used to investigate the influencing factors of gastric mucosal atrophy in elderly patients with HP infection and the interactive effects of the IL-23/Th17 immune-inflammatory axis and gut microbiota. Receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses were performed to assess the predictive value of the IL-23/Th17 immune-inflammatory axis and gut microbiota for gastric mucosal atrophy in elderly patients with HP infection. RESULTS: The study group had higher serum levels of IL-23, IL-17, TNF-α, IL-6, IL-2, and a higher count of Lactobacillus acidophilus, but lower counts of Bifidobacterium and Lactobacillus compared to the control group (P < 0.05). Within the study group, the atrophy subgroup showed more pronounced differences in these immunological and microbiological parameters compared to the non-atrophy subgroup (all P < 0.05). Logistic regression identified all measured immune factors and gut microbiota as independent influencing factors for gastric mucosal atrophy (all P < 0.05). Significant interactive effects were observed between the IL-23/Th17 axis factors and gut microbiota (all P < 0.05). The combined ROC model incorporating these factors achieved an AUC of 0.908 for predicting gastric mucosal atrophy, significantly outperforming individual predictors (all P < 0.001). CONCLUSION: There are significant interactive effects between the IL-23/Th17 immune-inflammatory axis and gut microbiota in gastric mucosal atrophy among elderly patients with HP infection, and the combined predictive value is reliable.
IL-2/IL-2Ab complexes expand regulatory T cells in vivo and provide neuroprotection after cardiac arrest.
Wu S, Chen X, Ling X … +3 more , Han Y, Chen S, Wang W
Immunol Lett · 2026 Apr · PMID 41297639 · Publisher ↗
Cardiac arrest (CA) results in global ischemia/reperfusion injury and severe neurological dysfunction, for which effective therapeutic interventions remain limited. Regulatory T cells (Tregs) play a crucial role in modul...
Cardiac arrest (CA) results in global ischemia/reperfusion injury and severe neurological dysfunction, for which effective therapeutic interventions remain limited. Regulatory T cells (Tregs) play a crucial role in modulating post-ischemic inflammation and promoting neuroprotection. In this study, we demonstrate that in vivo expansion of Tregs using the interleukin-2/interleukin-2 antibody (IL-2/IL-2Ab) complex significantly increased Treg numbers in the blood, spleen, and lymph nodes. Mice pretreated with the IL-2/IL-2Ab complex before cardiac arrest and cardiopulmonary resuscitation (CA/CPR) exhibited improved neurological recovery, reduced ischemic brain injury, and enhanced survival rates. These findings highlight a potential immunomodulatory strategy for improving outcomes after cardiac arrest. The IL-2/IL-2Ab complex may represent a promising adjunctive therapy to attenuate post-resuscitation brain injury through the selective expansion of protective Tregs.
Comparison of IgG antibody levels, avidity, and subclass distribution against pertussis toxin in children and adolescents after four-dose primary whole-cell (DTwP) or acellular (DTaP) vaccination, each followed by a single DTaP booster.
Rastawicki W, Zasada AA
Immunol Lett · 2026 Apr · PMID 41297638 · Publisher ↗
Vaccination plays a key role in the prevention of pertussis, the infectious disease that is endemic worldwide. Two types of pertussis vaccines are currently in use: whole-cell (wP) and acellular (aP) vaccines. Difference...
Vaccination plays a key role in the prevention of pertussis, the infectious disease that is endemic worldwide. Two types of pertussis vaccines are currently in use: whole-cell (wP) and acellular (aP) vaccines. Differences in the duration of immunity have been observed depending on the vaccine type. In this study, the levels of individual IgG subclasses and antibody avidity were assessed in children vaccinated with either aP or wP vaccines. The results revealed no significant differences in the mean IgG antibody levels and avidity between children immunised with wP and those who received aP vaccines. However, in the vaccinated children IgG4 was a dominated IgG subclass, regardless of vaccine used (aP v. wP), whereas in pertussis patients the IgG1 was dominating. These findings need deeper investigation, in terms of a vaccine efficacy and wanning immunity, as typically in response to protein antigens IgG1 is dominating. Moreover, the observation of IgG4 predominance in vaccinated vs. IgG1 predominance in infected individuals might be a valuable parameter in pertussis diagnostics as it enables differentiation between infected and vaccinated but not-infected individuals.
Letter to the editor: "Importance of BCG vaccination at birth in pediatric patients with chronic granulomatous disease after hematopoietic stem cell transplantation in developing countries".
Kumar S, Jesswani Y, Kumar M
Immunol Lett · 2026 Apr · PMID 41290118 · Publisher ↗
Abstract loading — click title to view on PubMed.
Dendritic Cells: key controllers of lymphoid tissue organization.
Calabrò A, De Pasquale C, Drommi F … +6 more , Giusto E, Tamburini S, Vento G, Yamazaki S, Campana S, Ferlazzo G
Immunol Lett · 2026 Apr · PMID 41241293 · Publisher ↗
Dendritic cells (DCs) are highly efficient antigen-presenting cells that play a central role in inducing and controlling immune responses. Beyond their role in antigen presentation and in orchestrating lymphocyte activit...
Dendritic cells (DCs) are highly efficient antigen-presenting cells that play a central role in inducing and controlling immune responses. Beyond their role in antigen presentation and in orchestrating lymphocyte activities, DCs also contribute to the spatial and functional organization of lymphoid structures, including both secondary and tertiary lymphoid organs, acting at different levels during both lymphoid tissue neogenesis and their maintenance. DCs can facilitate lymphoid tissue development by interacting with both lymphoid tissue inducer and organizer cells, initiating early aggregation and supporting lymphotoxin-mediated signaling pathways essential for lymphoid structure maturation. Additionally, DCs release chemokines attracting and anchoring immune cells in lymphoid tissues and regulate the formation and the overall size of high endothelial venule system, which mediate immune cell trafficking into lymphoid tissues. The dynamic crosstalk between DCs and fibroblastic reticular cells (FRC), which facilitate immune cell interactions and compartmentalization, is essential for lymphoid tissue specialization and function, though the precise cellular and molecular mechanisms of DC/FRC crosstalk remain to be fully elucidated. Finally, studies in mice and humans suggest that DC subsets are pivotal in T follicular helper cell differentiation, essential for humoral immunity in B cell follicles of lymphoid tissues, therefore emphasizing DCs' critical role also in supporting B cell maturation and antibody responses in the germinal centers of lymphoid organs.
Addressing the immunological gaps in asthma treatment: A call for region-specific research in Africa.
Alemayehu ZG, Sime BL, Keraga AS
Immunol Lett · 2026 Feb · PMID 41232612 · Publisher ↗
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Anti-Yo antibody associated axial movement disorders - a novel phenotype in ANNS.
Cherian A, K P D, R A … +1 more , K P D
Immunol Lett · 2026 Feb · PMID 41207392 · Publisher ↗
BACKGROUND: Movement disorders, as an anti-neuronal antibody mediated neurological syndrome(ANNS), is usually associated with anti-CV2/CRMP5,Hu/ANNA1 and Contactin-associated protein-like 2 (CASPR2) antibodies. Anti-Yo a...
BACKGROUND: Movement disorders, as an anti-neuronal antibody mediated neurological syndrome(ANNS), is usually associated with anti-CV2/CRMP5,Hu/ANNA1 and Contactin-associated protein-like 2 (CASPR2) antibodies. Anti-Yo antibody associated movement disorders are extremely rare. METHODS: We analysed the data of 47 patients with anti -Yo antibodies who presented over a period of 5 years (2019-2024) in a tertiary care institute. Those with movement disorder phenotype, without ataxia, were included. Other etiologies were excluded with relevant work up. RESULTS: We report two elderly males in their sixties who presented with a subacute onset isolated progressive axial movement disorders, with positive anti-Yo antibody. One patient with axial myoclonus and camptocormia who did not initially respond to intravenous methylprednisolone had remarkable improvement with intravenous immunoglobulin and rituximab, while in the other treatment response was suboptimal. CONCLUSION: Movement disorders due to anti-neuronal antibodies should be suspected when they develop subacutely, in older patients (> 50 years), have a progressive course beyond 3 months, associated with pain and constitutional symptoms like weight loss, all of which were present in our cases. Such intracellular Yo antigen induced ANNS usually have guarded response to immunomodulatory therapy compared to those mediated by antibodies against surface antigens, though one patient of ours had a remarkable improvement.
Siglec-1 macrophages in anti-tumor immunity.
Mauvais FX, van Endert P
Immunol Lett · 2026 Feb · PMID 41205710 · Publisher ↗
Macrophages expressing the sialic acid-binding lectin Siglec-1 are positioned strategically for uptake and filtering of antigenic material circulating through the lymphatic system into the subcapsular sinus of lymph node...
Macrophages expressing the sialic acid-binding lectin Siglec-1 are positioned strategically for uptake and filtering of antigenic material circulating through the lymphatic system into the subcapsular sinus of lymph nodes and through the blood into the marginal zone of the spleen. Siglec-1 macrophages are also found in many tissues, frequently displaying an inflammatory profile. In secondary lymphoid organs, these cells are strategically positioned and play a role in adaptive immune responses by B, NK and T lymphocytes. A potential role of the cells in antitumor immunity has attracted significant scientific interest. This concept is supported by a report of dendritic cell-independent priming of a protective antitumor response by lymph node Siglec-1+ macrophages. Indeed, examination of preclinical models and human tumors has provided evidence for a dominant protective effect of lymph node Siglec-1+ macrophages in major types of solid tumors e.g. breast or colorectal cancer. In contrast, Siglec-1+ macrophages within tumor tissue have been found to be associated variably with favorable or unfavorable outcome depending on the model and tumor studied. We have recently demonstrated in mouse models that splenic Siglec-1+ macrophages in themarginal zone can prime protective tumor immunity against both tumors disseminating through the blood and tumors invading the spleen in the absence of type 1 conventional dendritic cells. Considering this, we postulate Siglec-1+ macrophages in all secondary lymphoid organs can prime potent antitumor responses. We propose that this capacity could be exploited for therapeutic stimulation of tumor immunity.
PLIN2 exacerbates Allergic Rhinitis by inhibiting PINK1/Parkin-mediated mitophagy.
Yu W, Zhang S, Peng L … +1 more , Du J
Immunol Lett · 2026 Apr · PMID 41192682 · Publisher ↗
OBJECTIVE: To investigate the pro-inflammatory role and underlying mechanism of Perilipin 2 (PLIN2) in Allergic Rhinitis (AR), focusing on its regulation of PINK1/Parkin-mediated mitophagy and the subsequent impact on li...
OBJECTIVE: To investigate the pro-inflammatory role and underlying mechanism of Perilipin 2 (PLIN2) in Allergic Rhinitis (AR), focusing on its regulation of PINK1/Parkin-mediated mitophagy and the subsequent impact on lipid metabolism and oxidative stress. METHODS: Single-cell RNA sequencing (scRNA-seq) analysis was performed using GSE261706 from the GEO database, involving nasal mucosa from AR patients and healthy controls. A murine AR model was induced by ovalbumin (OVA), and human nasal epithelial cells (HNEpCs) were stimulated with Der p1. Interventions included AAV-mediated PLIN2 knockdown in vivo and siRNA-mediated knockdown in vitro. Techniques included Western blotting, qRT-PCR, flow cytometry, ELISA, and immunofluorescence/histological staining to assess PLIN2 expression, mitophagy, lipid accumulation, oxidative stress, and inflammatory responses. RESULTS: scRNA-seq analysis identified PLIN2 as a significantly upregulated gene in AR epithelial cells, which correlated with dysfunctional autophagy pathways. In both OVA-induced mice and Der p1-treated HNEpCs, PLIN2 expression was significantly elevated, accompanied by inhibited mitophagy (decreased LC3-II/I ratio, reduced PINK1/Parkin levels, and p62 accumulation), increased lipid deposition, and elevated ROS levels. PLIN2 knockdown markedly ameliorated AR pathology in mice, reducing inflammatory infiltration and serum levels of IgE, IL-4, and IL-5. Mechanistically, PLIN2 knockdown restored PINK1/Parkin-mediated mitophagy, decreased lipid accumulation, and attenuated ROS-induced cellular damage in HNEpCs. CONCLUSIONS: PLIN2 exacerbates AR pathogenesis by inhibiting PINK1/Parkin-mediated mitophagy, promoting lipid accumulation and oxidative stress, and ultimately causing cellular damage in nasal epithelial cells. PLIN2 acts as a pivotal mediator linking metabolic dysregulation to inflammation, highlighting it as a promising therapeutic target for AR treatment.
Human B-lymphopoiesis: Clinical challenges in B cell reconstitution and advances in in vitro modeling.
Schmidt FM, Rizzi M
Immunol Lett · 2026 Feb · PMID 41192681 · Publisher ↗
The B cell compartment is maintained by continuous replenishment from hematopoietic stem cells (HSCs) and multipotent progenitors, as well as from B cell precursors. B cell depletion is a common therapeutic approach, not...
The B cell compartment is maintained by continuous replenishment from hematopoietic stem cells (HSCs) and multipotent progenitors, as well as from B cell precursors. B cell depletion is a common therapeutic approach, not only in the context of B cell malignancies, but also in autoimmunity. The targeted elimination of B cells can be achieved through the use of chimeric antigen receptor (CAR)-T cells or monoclonal antibodies or bispecific antibodies that target both B and NK cells or B and T cells. When B cells are depleted, repopulation from bone marrow precursors occurs within three months to one year, following ontogeny. Nevertheless, prolonged B cell aplasia is observed in some patients and is associated with a progressive reduction of serum immunoglobulins and an increased susceptibility to infections. The mechanisms underlying such defects in B cell replenishment remain to be fully elucidated and studies on human B lymphopoiesis are needed in this context. Mouse models can be helpful in studying mechanisms of B cell development and the role of multiple (B cell-specific) genes in this process; however, they do not always mirror the human developmental dynamics and signals. Hence further tools are needed to study human B lymphopoiesis defects. In this review, we summarize the reported studies and cases of prolonged B cell aplasia following B cell depletion and discuss potential underlying causes. We then provide a comprehensive overview of the various in vitro models that can be used to study the dynamic of B lymphopoiesis to dissect B cell developmental defects in humans.
High complement expression on extracellular vesicles in Covid-19 patients without pulmonary embolism leading to death. Case report.
Taxiarchis A, Antovic J, Rooyackers O … +1 more , Dumitrescu G
Immunol Lett · 2026 Feb · PMID 41086954 · Publisher ↗
This case report analyzes two severe COVID-19 patients without pulmonary embolism, revealing persistently elevated levels of extracellular vesicles (EVs) carrying tissue factor (TF+), complement proteins (C3a+, TCC+), an...
This case report analyzes two severe COVID-19 patients without pulmonary embolism, revealing persistently elevated levels of extracellular vesicles (EVs) carrying tissue factor (TF+), complement proteins (C3a+, TCC+), and endothelial markers (CD144+, CD54+). Temporal trends in these EV subpopulations correlated with clinical deterioration, suggesting their role in endothelial injury, complement hyperactivation, and thromboinflammation. Notably, TF+EV dynamics aligned with anticoagulant treatment responses, while MPO+EVs reflected neutrophil activity without thrombotic complications. Despite differences in patient characteristics, these findings propose that patient-specific EV profiles may serve as potential indicators of disease progression, warranting targeted studies to validate their biomarker potential in severe COVID-19.
Herpesvirus entry mediator on effector memory CD8+ T cells mediates the effects of sterol ester (27:1/18:1) levels on critical sepsis.
Cai J, Li H, Cui W … +6 more , Hou M, Bo H, Zhang N, Wang Y, Zhu J, Tian C
Immunol Lett · 2026 Feb · PMID 41086953 · Publisher ↗
BACKGROUND: Lipid metabolism is closely associated with the development of sepsis; however, the relationship between specific lipid molecules and sepsis remains unclear, as does the extent to which immune cell traits med...
BACKGROUND: Lipid metabolism is closely associated with the development of sepsis; however, the relationship between specific lipid molecules and sepsis remains unclear, as does the extent to which immune cell traits mediate the effects of lipid levels on critical sepsis. OBJECTIVE: The effects of lipids on critical sepsis were examined in this work, along with the potential mediating function of immune cell characteristics in this process, using Mendelian randomization. MATERIALS AND METHODS: A comprehensive two-sample Mendelian randomization analysis was conducted using genetic data from a genome-wide association study of 179 lipids, a large-scale genome-wide association study of 731 immune cell traits, and the latest genome-wide association study of critical sepsis. The ratios of immune cell trait indirect and mediating effects were computed using the coefficient product approach. RESULTS: We identified 4 lipids and 18 immune cell traits that had a negative causal relationship with critical sepsis, and 1 lipid and 13 immune cell traits that had a positive causal relationship with critical sepsis. Herpesvirus entry mediator (HVEM) on effector memory CD8+ T cells mediates the effects of sterol ester (27:1/18:1) levels on critical sepsis, accounting for 6.1% of this effect. CONCLUSION: Our study confirmed the genetic causal relationship between lipids, immune cell traits, and critical sepsis, highlighting the potential mediating role of HVEM on effector memory CD8+ T cells and providing insights that may aid in the development of strategies for the prevention and treatment of critical sepsis in the clinic.
The essential integration of sex and gender in immunological research.
Altfeld M, Consiglio C, Duffy D … +5 more , Ingersoll M, O'Farrelly C, Pecht T, Shay T, Soares H
Immunol Lett · 2026 Feb · PMID 41076099 · Publisher ↗
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Environmental determinants of immune tolerance in asthma and allergy.
Karisola P, Alenius H
Immunol Lett · 2026 Feb · PMID 41076098 · Publisher ↗
Prevalence of allergic diseases has increased globally, reflecting environmental and behavioral changes. The exposome concept encompasses cumulative chemical, microbial, nutritional, psychosocial, and physical exposures...
Prevalence of allergic diseases has increased globally, reflecting environmental and behavioral changes. The exposome concept encompasses cumulative chemical, microbial, nutritional, psychosocial, and physical exposures across the life course, offering a unifying framework to understand how immune tolerance is shaped or disrupted. Emerging evidence highlights that early-life exposures are particularly critical. Pollutants, endocrine disruptors, microbial deprivation, dietary shifts, and psychosocial stress contribute to barrier dysfunction, dysbiosis, and immune dysregulation, favoring Th2 dominance and allergy development. In contrast, exposures that enhance biodiversity, microbial diversity, pollution-free air, and balanced nutrition support active tolerance development, especially via regulatory T cells. Mechanistic insights point to the barrier-microbiota-immune axis as central pathways linking the environment to allergic outcomes. Translational studies, including biodiversity enrichment interventions, maternal and infant dietary strategies, and microbiome-based therapies, illustrate the potential of exposome-informed approaches to allergy prevention. However, major challenges remain in measuring complex exposure mixtures, identifying causal pathways, and integrating exposome data with systems immunology. This review synthesizes current knowledge on how the exposome modulates immune tolerance and outlines future research directions toward precision prevention. A deeper understanding of these interactions is essential to address the rising global allergy burden.
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