Immunol Lett
· 2025 Jun · PMID 39924005
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Antibodies of the IgE and IgG1 isotypes are relevant for type 2 immunity. In vivo, the production of both is elevated by IL-4, but differentially affected by IL-21, with IgE suppressed and IgG1 production enhanced by IL-...Antibodies of the IgE and IgG1 isotypes are relevant for type 2 immunity. In vivo, the production of both is elevated by IL-4, but differentially affected by IL-21, with IgE suppressed and IgG1 production enhanced by IL-21. However, whether the cytokines drive these outcomes primarily by impacting antibody-secreting, proliferating plasmablasts (PB), or their germinal center B cell precursors, is challenging to unravel. In vitro analyses using Nojima cultures, wherein naïve B cells are activated on fibroblasts co-expressing CD40L and BAFF, allows for evaluation of this problem. Here, we explore how IL-4 and IL-21 alone and in combination affect Nojima-cultured B cell proliferation and fate, asking what is unique or redundant about exposure to each. In secondary culture, as expected, IL-21 amplified replicative expansion. IL-21 also selectively promoted the differentiation of IgG1 B cells into PB. The effect was countermanded by synchronous exposure to IL-4, suggesting competing signaling pathways are triggered by the two cytokines independently. Secondary culture with IL-4 alone promoted IgE B cell genesis without increasing replicative expansion. Combined exposure to IL-21 and IL-4 led to increased IgE class-switching and proliferative expansion, suggesting that once B cells are switched to IgE, IL-21 can promote IgE+ B cell proliferation. Thus, in culture IL-21 operates to promote proliferation and also drives differentiation of IgG1+ B cells into PB whereas IL-4 has an ongoing role in IgE B cell genesis. The balance of IL-4 and IL-21 thus impacts the fate of in vitro-generated germinal center B cells and highlights how the notable IgE-suppressing effects of IL-21 in vivo likely precede the class-switch step, after which IL-21 may amplify IgE production by virtue of its pro-proliferative effects.
Corona-Cervantes K, Sánchez-Salguero E, Zárate-Segura PB
… +9 more, Krishnakumar A, Piña-Escobedo A, Rangel-Calvillo MN, Ramírez-Lozada T, Acosta-Altamirano G, Lázaro-Pérez NDS, Sierra-Martínez M, Santos-Argumedo L, García-Mena J
Immunol Lett
· 2025 Jun · PMID 39924004
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In the early days, maternal immunoglobulins are essential for sustaining a balanced gut environment by influencing the interaction between the host and the microbiome. The successional establishment of the pioneer strain...In the early days, maternal immunoglobulins are essential for sustaining a balanced gut environment by influencing the interaction between the host and the microbiome. The successional establishment of the pioneer strains is an interesting topic of research where maternal immunoglobulins appear to be important. This proof-of-concept study explored the binding pattern of IgA1, IgA2, IgM, and IgG classes to a commensal bacterial in human colostrum and the stool of breastfed neonates. We used flow cytometry coupled with 16S rRNA gene sequencing in human colostrum and neonatal feces samples to characterize this Ig-microbiota association. We observed that in human colostrum samples, IgA2 and IgM bind alfa and beta Proteobacteria, which can potentially stimulate neonatal immune system development in the gut. Other immunoglobulins like IgG predominantly bind facultative anaerobes belonging to the Firmicutes phylum, reported as part of human milk microbiota and pioneer colonizers of the neonatal gut. Maternal immunoglobulins also bind a wide diversity of bacteria in the neonatal stool. For instance, IgA2 and IgM bound more members of the phylum Bacteroidetes in comparison to IgG, these Bacteroidetes and some firmicutes have been reported as late colonizers of the neonatal gut, and their presence is important due to their ability to produce important short chain fatty acids like propionate and butyrate. Our results support the current view that microbial and immunoglobulin transference is crucial for developing the neonate's immune system and individual gut microbiota.
This study investigates the role of the STING signaling pathway in enhancing dendritic cells (DCs) maturation and activation in response to the hepatitis B vaccine. By analyzing the GSE52894 dataset, we compared differen...This study investigates the role of the STING signaling pathway in enhancing dendritic cells (DCs) maturation and activation in response to the hepatitis B vaccine. By analyzing the GSE52894 dataset, we compared differentially expressed genes between mature dendritic cells (mDCs) and immature dendritic cells (iDCs). In vitro, iDCs were treated with the STING agonist 2'3'-cGAMP, either alone or in combination with lipopolysaccharide (LPS) or the hepatitis B vaccine, to assess the expression of costimulatory molecules and key signaling molecules in the STING pathway, including STING, pNF-κBp65, and pIRF3. The results indicated that mDCs expressed significantly higher levels of STING mRNA compared to iDCs (P < 0.01). Treatment with 2'3'-cGAMP increased STING expression and activated downstream signaling molecules pNF-κBp65 and pIRF3. Co-treatment with 2'3'-cGAMP and LPS upregulated costimulatory molecules (CD80, CD86, HLA-DR, CD11c) more effectively than LPS alone (P < 0.05). Co-treatment with 2'3'-cGAMP and the hepatitis B vaccine resulted in significantly higher expression of costimulatory molecules compared to vaccine-only treatment. Furthermore, co-treatment with 2'3'-cGAMP and the hepatitis B vaccine enhanced STING, pNF-κBp65, and pIRF3 expression relative to vaccine alone. Mixed lymphocyte reaction assays demonstrated that the 2'3'-cGAMP and hepatitis B vaccine co-treatment group had a significantly stronger effect on the proliferation of CD4T cells compared to the vaccine-only treatment group. In conclusion, 2'3'-cGAMP enhances DCs maturation and promotes CD4T cells proliferation in response to the hepatitis B vaccine by activating the STING/IRF3 and STING/NF-κB pathways, highlighting its potential as an adjuvant to improve vaccine efficacy.
Plastics are everywhere. It is widely recognized that they represent a global problem, the extent of which is yet to be defined. Humans are broadly exposed to plastics, whose effects and consequences are poorly character...Plastics are everywhere. It is widely recognized that they represent a global problem, the extent of which is yet to be defined. Humans are broadly exposed to plastics, whose effects and consequences are poorly characterized so far. The main route of exposure is via alimentary and respiratory intake. Plastics pollutions may come from both: water and food contamination itself, and their packaging. The smaller sizes (i.e. microplastics <150 µm - MPs) are considered to be the most pervasive of living organisms and, therefore, potentially the most harmful. As humans occupy one of the apex positions of the food chain, we are exposed to bioaccumulation and biomagnification effects of MPs. In fact, MPs are commonly found in human stools and blood. However, there are no data available yet on their ability to accumulate and to produce detrimental consequences on biological systems. Even though the effects of plastics pollution are poorly studied in mammals, including humans, they appear to have inflammatory effects, which is rather concerning as many etiologies of disease are based on a pro-inflammatory status.
Natori Y, Martin E, Mattiazzi A
… +12 more, Arosemena L, Burke GW, Munagala MR, Manickavel S, Sota K, Pallikkuth S, Chen J, Bini J, Simkins J, Anjan S, Vianna RM, Guerra G
Immunol Lett
· 2025 Jun · PMID 39798807
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INTRODUCTION: In Solid Organ Transplant (SOT) recipients, due to immunosuppression, the immunogenicity after COVID-19 vaccination is suboptimal and its durability is unknown. METHODS: We conducted a post-hoc analysis of...INTRODUCTION: In Solid Organ Transplant (SOT) recipients, due to immunosuppression, the immunogenicity after COVID-19 vaccination is suboptimal and its durability is unknown. METHODS: We conducted a post-hoc analysis of a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs JNJ-78,436,735 as the third dose after two doses of BNT162b2 in adult SOT recipients with active graft to compare long-term immunogenicity. RESULTS: Forty-one recipients were analyzed. Median IgG levels against SARS-CoV-2 at 6 months were 53,747 (range 949 - 657,558) and 7,632 (range 642 - 672,000) AU/ml for BNT162b2 vs JNJ-78,436,735, respectively (p = 0.017). The median geometric mean fold increase ratio at 6 months was 37.2 (0.12-618.5) and 4.30 (0.1-204.2) for BNT162b2 vs JNJ-78,436,735, respectively (p < 0.05). After two doses of BNT162b2, homologous approach with BNT162b2 achieved a superior immunogenicity compared to heterologous approach with JNJ-78,436,735. CONCLUSION: In this post hoc analysis, we report durability of specific IgG between two vaccine strategies and found no statistically significant difference between two groups. (Clinical Trial Registry: NCT05047640).
Tumor-associated macrophages (TAMs) play crucial roles in development and progression of malignant diseases. Notably, CD163 TAMs likely perform specific pro-tumorigenic functions, suggesting that this subset may serve as...Tumor-associated macrophages (TAMs) play crucial roles in development and progression of malignant diseases. Notably, CD163 TAMs likely perform specific pro-tumorigenic functions, suggesting that this subset may serve as both prognostic biomarkers and targets for future anti-cancer therapy. We conducted a scoping review to map the current knowledge on the prognostic role of CD163 TAMs in the five most lethal cancers worldwide: Lung, colorectal, gastric, liver, and breast cancer. For all cancer types, most studies showed that high tumoral presence of CD163 cells was associated with poor patient outcome, and this association was more frequently observed when CD163 cells were measured at the tumor periphery compared to more central parts of the tumor. These results support that CD163 TAMs represent a biomarker of poor patient outcome across a variety of solid tumors, and highlight the relevance of further investigations of CD163 TAMs as targets of future immunotherapies.
(1) BACKGROUND: Metabolic abnormalities and immune inflammation are key elements within pathogenesis of pulmonary arterial hypertension (PAH). And in PAH patients, aberrant glutamine metabolism has been observed; however...(1) BACKGROUND: Metabolic abnormalities and immune inflammation are key elements within pathogenesis of pulmonary arterial hypertension (PAH). And in PAH patients, aberrant glutamine metabolism has been observed; however, the function of glutaminase 1 (GLS1) in macrophage is still unknown. So we aims to investigate GLS1's impact upon macrophages in PAH. (2) METHODS: We firstly constructed an monocrotaline (MCT)-induced PAH rat model. Briefly, the PAH rats were treated with the GLS1 inhibitor BPTES, and various index were evaluated, including hemodynamics, right ventricular function, pulmonary vascular remodeling, macrophage markers, and glutamine metabolism. After that, we polarized bone marrow-derived macrophages (BMDMs) into M1 phenotype and then subjected to BPTES intervention. Finally, we assessed macrophage phenotype, inflammatory markers, and glutamine metabolism indicators, along with the impact of BMDM supernatant on the behavior of pulmonary arterial smooth muscle cells (PASMCs). (3) RESULTS: GLS1 was significantly upregulated in both PAH patients and rats. Treatment with the GLS1 inhibitor BPTES markedly improved pulmonary arterial pressure, right ventricular function, and pulmonary vascular remodeling in PAH rats, while inhibiting M1 macrophage polarization, NLRP3 activation, and the release of pro-inflammatory cytokines. This, in turn, alleviated the proliferation and migration of PASMCs induced by inflammatory stimuli. (4) CONCLUSION: We propose that targeting GLS1 to reduce M1 macrophage polarization and inflammatory responses may represent a promising therapeutic approach for PAH.
While much is known about the expression of interferon (IFN) pathways in the blood of people living with HIV (PLWH), their role in the intesinal tract has only recently been appreciated. The aim of this study was to eval...While much is known about the expression of interferon (IFN) pathways in the blood of people living with HIV (PLWH), their role in the intesinal tract has only recently been appreciated. The aim of this study was to evaluate gut mRNA expression levels of innate immune genes involved in the HIV-host interaction and their association with CD4T cell immune activation in long-term HAART-experienced PLWH. PLWH had increased intestinal levels of TLR4, type I IFN (IFN-α2, IFN-α14, IFN-β) and IFNAR1 mRNAs, as well as increased frequencies of CD4T lymphocytes expressing CD38 or HLA-DR compared to the healthy donors. Moreover, TLR4, TLR9, IRF3, IRF7 and IFN-α14 mRNA expression was positively correlated with the frequency of CD4T cells expressing CD38 or HLA-DR. These findings suggest a dysregulation of innate immunity, particularly of the TLRs and IFN pathways in the gut of PLWH. Genes in these pathways also appear to correlate with the levels of CD4T cell immune activation.
Probiotics have been increasingly recognized for positively influencing many aspects of human health. Lactiplantibacillus plantarum (L. plantarum), a non-pathogenic bacterium, previously known as Lactobacillus plantarum,...Probiotics have been increasingly recognized for positively influencing many aspects of human health. Lactiplantibacillus plantarum (L. plantarum), a non-pathogenic bacterium, previously known as Lactobacillus plantarum, is one of the lactic acid bacteria commonly used in fermentation. The probiotic properties of L. plantarum have highlighted its health benefits to humans when consumed in adequate amounts. L. plantarum strains primarily enter the body orally and alter intestinal microflora and modulate the immune responses in their host; thereby benefiting human health. Furthermore, the use of L. plantarum as vaccine vectors delivering mucosal antigens has been shown to be a promising strategy. These aspects, from Immunomodulation to vaccine delivery by L. plantarum in preclinical settings, are highlighted in this review. Along these lines, construction of a recombinant L. plantarum strain expressing a B cell multi-peptide, as a future vaccine to modulate immunity and confer anti-tumor effect by targeting Her-2/neu-overexpressing cancers in local and distal sites, is also presented and discussed.
BACKGROUND: Diabetic retinopathy (DR) is a common complication of diabetes, which may cause visual disturbance and even loss of sight. Oxidative stress and inflammation are two crucial pathological factors of DR; however...BACKGROUND: Diabetic retinopathy (DR) is a common complication of diabetes, which may cause visual disturbance and even loss of sight. Oxidative stress and inflammation are two crucial pathological factors of DR; however, their specific regulatory mechanisms in DR remain obscure. METHODS: DR models were established in streptozotocin-challenged rats and high glucose (HG)-stimulated Müller cells. Western blotting and RT-qPCR were performed to determine target molecule levels. ROS release was evaluated by DCFH-DA staining, and the levels of MDA, GSH, SOD, and CAT were detected using commercial kits. The levels of proinflammatory factors (TNF-α, IL-1β, IL-6, MCP-1, and CXCL-1) were analyzed by RT-qPCR and ELISA. The subcellular localization of OGRU was observed by FISH. Molecular interaction was evaluated by RIP. M6A level was assessed by MeRIP and colorimetric quantification kit. RESULTS: HG stimulation or diabetic stress resulted in an elevation in the overall m6A level, as well as expression level of methyltransferase-like 3 (METTL3) in the experimental models of DR. M6A writer METTL3 stabilized lncRNA OGRU via m6A modification. Functionally, METTL3 deficiency relieved HG-induced oxidative stress damage and inflammation in Müller cells. Rescue assays demonstrated that OGRU overexpression reversed METTL3 silencing-mediated protection against HG-stimulated Müller cells. Furthermore, YTH Domain-Containing Protein 1 (YTHDC1) coordinated with METTL3 to enhance OGRU stability in an m6A-dependent manner. CONCLUSION: METTL3-mediated m6A modification stabilized OGRU with assistance of YTHDC1, which led to oxidative stress and inflammation during DR progression. Targeting METTL3/YTHDC1/OGRU axis might be a potential therapeutic strategy for DR.
BACKGROUND: The spleen, as the body's largest peripheral immune organ and a crucial source of circulating monocytes, plays a significant role in the acute inflammatory response of spleen-derived macrophages to diseases....BACKGROUND: The spleen, as the body's largest peripheral immune organ and a crucial source of circulating monocytes, plays a significant role in the acute inflammatory response of spleen-derived macrophages to diseases. Therefore, studying the impact and mechanism of X-ray irradiation on spleen-derived macrophages' inflammatory responses is of great importance. METHOD: Extracted and identified mice splenic macrophages were divided into four groups: control group, LPS and ATP co-stimulated non-irradiated group, LPS and ATP co-stimulated group irradiated after 6 h, and LPS and ATP co-stimulated group irradiated after 12 h In the LPS and ATP co-stimulated groups, LPS (1μg/ml) and ATP (5mmol/L) were added to establish an inflammatory model in mice splenic macrophages. The irradiated groups were exposed to a medical linear accelerator (Elekta Synergy), while the non-irradiated groups were placed under the light source for the same duration without irradiation. Protein extraction was performed in each group at 6 h and 12 h post-treatment for subsequent analysis using Western blot, ELISA, RT-qPCR and other relevant methods. RESULTS: (1) Compared with the non-irradiated group, the cell activity in the groups irradiated for 6 h and 12 h at 8 Gy showed a significant increase (P<0.01). (2) In the LPS and ATP co-stimulated groups irradiated after 6 h and 12 h, the expression of NLRP3 mRNA and protein, IL-18 and IL-1β showed a notable decrease compared to the LPS and ATP co-stimulated non-irradiated group (P<0.05). Additionally, caspase-1 expression of caspase-1 mRNA and protein in the 12 h post-irradiation group also decreased considerably when compared with the LPS and ATP co-stimulated non-irradiated group (P < 0.05). In the groups irradiated after 6 h and 12 h, (3) there was a remarkable decrease in the expression of TWIK mRNA and TWIK2, (4) as well as Gq mRNA and protein, when compared to the LPS and ATP co-stimulated non-irradiated group (P < 0.05). Particularly, the 12 h post-irradiation group exhibited a notable reduction in PKC expression (P < 0.05). CONCLUSION: X-ray irradiation is capable of inhibiting the activation of ATP-dependent NLRP3 inflammasomes in splenic macrophages.
OBJECTIVE: Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of systemic autoimmune disorders affecting skeletal muscles but also other organs. There are different forms of IIM, each with peculiar clinic...OBJECTIVE: Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of systemic autoimmune disorders affecting skeletal muscles but also other organs. There are different forms of IIM, each with peculiar clinical manifestations and prognosis. Accordingly, several autoantibodies have been described in IIM, with different prevalence in the different forms of the disease. The etiopathogenesis of IIM is still unclear, although environmental agents play certainly a role to trigger disease development in genetically predisposed individuals. Supporting this notion, some reports suggest that the incidence of IIM may be different throughout the year. In this work, we tested if the detection of autoantibodies typically observed in IIM has a seasonal pattern. METHODS: We collected serological data from line immunoassays (LIA) performed on 4277 patients with suspected IIM from January 2018 to December 2020 in ten Italian hospitals. Myositis-specific and myositis-associated autoantibodies were evaluated by line-immunoassay. RESULTS: Our findings demonstrate that absolute numbers of anti-MDA5, anti-PM-Scl75, anti-Mi2b and anti-TIF1ɣ autoantibodies are more frequently detected in autumn-winter than in spring-summer. However, only anti-PM-Scl75 and anti-MDA5 display a similar pattern when analyzing frequencies of positive tests (for anti-PM-Scl75 100 positive tests and 2107 negative tests from September to February; 55 positive tests and 1903 negative tests from March to August, p = 0.003; for anti-MDA5 34 positive tests and 1983 negative tests from September to February; 17 positive tests and 1760 negative tests from March to August, p = 0.051). CONCLUSIONS: These findings suggests that triggering agents promoting the development of these autoantibodies have a specific seasonal pattern.
Azimnasab-Sorkhabi P, Soltani-Asl M, Bouhajra M
… +2 more, Ansa-Addo EA, Junior JRK
Immunol Lett
· 2024 Dec · PMID 39667581
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Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a receptor that inhibits the activity of T cells. The CTLA-4 gene consists of four different exons that enable four different isoforms of CTLA-4 to be generated thr...Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a receptor that inhibits the activity of T cells. The CTLA-4 gene consists of four different exons that enable four different isoforms of CTLA-4 to be generated through alternative splicing. Although sCTLA-4 might impede the therapeutic effect of anti-CTLA-4 treatments, the role of sCTLA-4 in the tumor microenvironment (TME) is not well understood. Here, we provide novel perspectives on the inhibitory characteristics of sCTLA-4 in TME.
La Gualana F, Olivieri G, Petriti B
… +12 more, Picciariello L, Natalucci F, Sciannamea M, Gragnani L, Basile U, Casato M, Spinelli FR, Stefanini L, Basili S, Visentini M, Ceccarelli F, Conti F
Systemic lupus erythematosus (SLE) is characterized by B cell dysregulation and expansion of atypical B cells that may correlate with disease manifestations and activity. This study investigated the impact of subcutaneou...Systemic lupus erythematosus (SLE) is characterized by B cell dysregulation and expansion of atypical B cells that may correlate with disease manifestations and activity. This study investigated the impact of subcutaneous (sc) Belimumab (BLM) on the peripheral B cell compartment and on the functional properties of CD21, T-bet and CD11c atypical B cells, in 21 active SLE patients over a 12-month period. At baseline, active SLE patients displayed reduced unswitched IgM memory B cells and expansion of atypical B cells, compared to healthy donors and to SLE patients in remission. sc BLM therapy promptly restored B cell homeostasis with a reduction of T-bet B cells, observed early in patients responsive to therapy. These findings highlight the pathogenic role of T-bet B cells in SLE disease and suggest their potential utility as biomarker of clinical response.
OBJECTIVE: The function and mechanism of NOD-like receptor family CARD-containing 3 (NLRC3) in psoriasis are not yet reported, even though it plays a crucial role in innate and adaptive immunity by inhibiting inflammatio...OBJECTIVE: The function and mechanism of NOD-like receptor family CARD-containing 3 (NLRC3) in psoriasis are not yet reported, even though it plays a crucial role in innate and adaptive immunity by inhibiting inflammation. Therefore, this research aims to investigate the role and mechanism of NLRC3 in psoriasis. METHODS: HaCaT cells were induced to form a psoriasis cell model using 20 ng/mL IL-1β, 20 ng/mL IL-17A, 20 ng/mL IL-23, 50 ng/mL TNF-α, and 20 ng/mL oncostatin M. Cell Counting Kit-8 (CCK-8) assay and flow cytometry were assessed to determine the proliferation, cell cycle, and apoptosis of HaCaT cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized to measure the knockdown efficiency of NLRC3 and TRAF6 interfering RNA in HaCaT cells. Western blot analysis was performed to determine the expression levels of NLRC3, TRAF6, and proteins associated with the NF-κB signaling pathway. A mouse model of psoriasis-like dermatitis was established by evenly applying miquimod cream (62.5 mg/day) to both ears. Hematoxylin-eosin staining was used to measure ear thickness and inflammatory infiltrates in mice. Histological analysis, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL were performed to detect cell proliferation and apoptosis. Interactions between NLRC3 and TRAF6 were predicted using the STRING database (https://cn.string-db.org/). Co-Immunoprecipitation was used to confirm interactions between NLRC3 and TRAF6. Ubiquitination of TRAF6 was assessed by Western blot. RESULTS: Knockdown of NLRC3 expression promoted cell proliferation and inhibited cell apoptosis in HaCaT cells. In vivo, knockdown of NLRC3 expression significantly increased the infiltration of inflammatory cells and the proliferation of Ki-67 positive cells within mouse ear epidermis, while decreasing the number of apoptotic cells. NLRC3 interacted with TRAF6 and influenced its K63 ubiquitination level. Knockdown of TRAF6 expression resulted in increased cell proliferation and decreased cell apoptosis in HaCaT cells. In vivo, knockdown of TRAF6 expression led to a significant increase in inflammatory cell infiltration and Ki-67 positive cells in mouse ear epidermis, and a decrease in apoptotic cells. Inhibiting the NF-κB signaling pathway alleviated the progression of psoriasis, and interfering with TRAF6 activated the NF-κB signaling axis, contributing to the onset and advancement of psoriasis. CONCLUSION: NLRC3 affects the occurrence of psoriasis by regulating TRAF6 and influencing the NF-κB signaling axis-mediated inflammatory response. This finding offers a theoretical foundation for the treatment of psoriasis.
Chen Z, Zeng A, Yang P
… +5 more, Zhang J, Liu D, Li M, Jing F, Yi Q
Immunol Lett
· 2025 Feb · PMID 39603426
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OBJECTIVE: To elucidate the relationship between leukocyte-associated Ig-like receptor-1 (LAIR-1) and the pathogenesis of Kawasaki disease (KD) and coronary artery aneurysms(CAA). METHODS: The study cohort comprises chil...OBJECTIVE: To elucidate the relationship between leukocyte-associated Ig-like receptor-1 (LAIR-1) and the pathogenesis of Kawasaki disease (KD) and coronary artery aneurysms(CAA). METHODS: The study cohort comprises children who were diagnosed with KD and were categorized into two groups: KD patients with CAA (KD-CAA) and KD without CAA (KD-NCAA), with healthy children serving as control group (HC). LAIR-1 on leukocytes was examined via flow cytometry, while serum LAIR-1 (sLAIR-1) was quantified using ELISA. IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-α, IFN-γ and TNF-α were examined by Immunofluorescence assay. RESULTS: sLAIR-1 levels were elevated in the KD and KD-CAA groups compared with those in the HC and KD-NCAA groups (P < 0.05). sLAIR-1 exhibited an area under the curve value of 0.858 for predicting KD (P < 0.001) and 0.628 for predicting CAA (P = 0.055, borderline significance). LAIR-1 was increased on the neutrophils in KD group, whereas it was lower in KD-CAA than that in KD-NCAA, and decreased in KD after IVIG treatment. In contrast, LAIR-1 was reduced on CD4+ and CD8+ T lymphocyte in KD group, and increased in KD after IVIG treatment (all P < 0.05). LAIR-1 on neutrophils showed a positive correlation with IL-5, while on CD4+ T cells, it was negatively correlated with IL-2, IL-6, IL-10, IFN-γ, and IL-8. On CD8+ T cells, LAIR-1 was negatively correlated with IL-2 and IFN-γ. CONCLUSION: sLAIR-1 may serve as a potential biomarker for KD and CAAs, while LAIR-1 might be implicated in KD pathogenesis and CAA.
Miyazaki A, Yoshida S, Takeda Y
… +3 more, Tomaru U, Matsumoto M, Seya T
Immunol Lett
· 2025 Feb · PMID 39603425
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Radiation therapy (RT) rarely induces tumor regression at untreated metastatic sites, the so-called abscopal effect. A syngeneic tumor (EG7) transplanted into a Th1-dominant mouse strain (C57BL/6) regressed significantly...Radiation therapy (RT) rarely induces tumor regression at untreated metastatic sites, the so-called abscopal effect. A syngeneic tumor (EG7) transplanted into a Th1-dominant mouse strain (C57BL/6) regressed significantly on the treated side and less on the contralateral side after RT. Additional subcutaneous administration of ARNAX, a non-inflammatory adjuvant, further accelerated tumor regression on the untreated side. This suggests that ARNAX after RT significantly enhances the tumor regression effect on the irrelevant tumor. Based on this setting, we next observed similar tumor shrinkage after RT and ARNAX by transplanting syngeneic breast cancer tumors (4T1) into a Th2-dominant mouse strain (BALB/c). The results were as follows: 1. ARNAX enhanced RT-mediated tumor shrinkage comparable to polyI:C; 2. In the Th2 mouse strain, little tumor regression occurred on the untreated side compared to tumor regression on the treated side after RT alone; 3. RT+ARNAX treatment caused additive regression on the treated side and induced slight tumor regression on the untreated side; 4. PD-L1 antibody + RT combination therapy caused tumor regression and further induced additive regression with ARNAX; 5. The combination of RT and ARNAX reduced the number and volume of lung metastases compared to RT alone. However, tumor regression was not always accompanied by a significant prolongation of survival in the mice receiving our regimen and protocol (one 10Gy radiation and a single ARNAX treatment). In conclusion, RT therapy promoted abscopal tumor regression in both Th2 and Th1 models with the addition of the non-inflammatory adjuvant ARNAX.
de Vreugd A, Zimmermann FA, Steinbrücker K
… +5 more, de Vries MC, de Boer L, Janssen MC, Huemer M, Wortmann SB
Immunol Lett
· 2025 Feb · PMID 39557131
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We here explore adverse events following immunization (AEFI) in children with mitochondrial disease (MD) recruited from two expertise centers in Austria (SALK) and The Netherlands (RUMC). Parents completed a questionnair...We here explore adverse events following immunization (AEFI) in children with mitochondrial disease (MD) recruited from two expertise centers in Austria (SALK) and The Netherlands (RUMC). Parents completed a questionnaire on the type of immunizations received and AEFI in a post-vaccination exposure period of seven days. 95 individuals were invited to this study, of whom 30 (median age 13.4 years) participated. Together these individuals had received 376 immunizations with a median of 12 vaccinations each. In 316 of 376 (84 %) vaccinations no AEFI occurred, 22 patients (73 %) never experienced any AEFI. Eight patients experienced 76 AEFI after 60 vaccinations, these were mild (redness (n = 9) /pain at injection site (n = 21), fever (n = 44), gastrointestinal complaints (n = 2)). None had a metabolic deterioration or seizures, no patient was admitted to the hospital. Although our data is limited by the small sample size, this may aid in discussing responsible immunization decisions with parents.