Clinical immunology最新文献

{"title":"T peripheral helper (Tph) cells, a marker of immune activation in cancer and autoimmune disorders","authors":"Celia del Carmen Crespo Oliva ,&nbsp;Marilyne Labrie ,&nbsp;Hugues Allard-Chamard","doi":"10.1016/j.clim.2024.110325","DOIUrl":"10.1016/j.clim.2024.110325","url":null,"abstract":"<div><p>T peripheral helper (Tph) cells are a newly discovered subtype of CD4+ T cells that have emerged as the counterpart of T follicular helper (Tfh) cells in the peripheral tissues. These two cell types share some common characteristics, such as high levels of PD1 and CXCL13 expression, but differ in the expression of transcription factors and chemokine receptors. Tph cells have been studied in relation to B cells' effector functions, including cytokines production and antibody-mediated immune responses. However, their role in the inflammatory-mediated development of malignancies remains poorly understood. Tph cells were initially identified in the synovium of rheumatoid arthritis patients and have since been found to be expanded in several autoimmune diseases. They have been linked to a worse prognosis in autoimmune conditions, but intriguingly, their presence has been correlated with better outcomes in certain types of cancer. The functions of Tph cells are still being investigated, but recent data suggests their involvement in the assembly of tertiary lymphoid structures (TLS). Furthermore, their interaction with B cells, which have been mainly described as possessing a memory phenotype, promotes their development. In this review, we explore the role of Tph cells in peripheral immune responses during cancer and autoimmune disorders.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110325"},"PeriodicalIF":4.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624004340/pdfft?md5=9c1fe539a3be3c90c526f1d522650d25&pid=1-s2.0-S1521661624004340-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel hypermorphic variants in IRF2BP2 identified in patients with common variable immunodeficiency and autoimmunity","authors":"Manfred Anim ,&nbsp;Georgios Sogkas ,&nbsp;Nadezhda Camacho-Ordonez ,&nbsp;Gunnar Schmidt ,&nbsp;Abdulwahab Elsayed ,&nbsp;Michele Proietti ,&nbsp;Torsten Witte ,&nbsp;Bodo Grimbacher ,&nbsp;Faranaz Atschekzei","doi":"10.1016/j.clim.2024.110326","DOIUrl":"10.1016/j.clim.2024.110326","url":null,"abstract":"<div><p>The interferon regulatory factor 2 binding protein 2 (IRF2BP2) is a transcriptional regulator, functioning a transcriptional corepressor by interacting with the interferon regulatory factor-2. The ubiquitous expression of IRF2BP2 by diverse cell types and tissues suggests its potential involvement in different cell signalling pathways. <strong>Variants in</strong> <em>IRF2BP2</em> <strong>have been recently identified to cause familial common variable immunodeficiency (CVID) characterized by immune dysregulation.</strong></p><p>This study investigated three rare novel variants <strong>in</strong> <em>IRF2BP2</em><strong>,</strong> identified in patients with primary antibody deficiency and autoimmunity by whole exome-sequencing (WES). Following transient overexpression of EGFP-fused mutants in HEK293 cells and transfection in Jurkat cell lines, we used fluorescence microscopy, real-time PCR and Western blotting to analyze their effects on IRF2BP2 expression, subcellular localization, nuclear translocation of IRF2, and the transcriptional activation of NFκB1(p50).</p><p>We found altered IRF2BP2 mRNA and protein expression levels in the mutants compared to the wild type after IRF2BP2 overexpression. In confocal fluorescence microscopy, variants in the C-terminal RING finger domain showed an irregular aggregate formation and distribution instead of the expected nuclear localization compared to the variants in the N-terminal zinc finger domain and their wildtype counterpart. Immunoblotting revealed an impaired IRF2 and NFκB1 (p50) nuclear localization in the mutants compared to the IRF2BP2 wildtype counterpart. LPS stimulation reduced IRF2BP2 mRNA expression in the variants compared to the wild type.</p><p>Our findings significantly contribute to understanding the clinical significance of <em>IRF2BP2</em> mutations in the pathogenesis of immunodeficiency and immune dysregulation. We observed impairment of the nuclear translocation of IRF2 and NFκB1 (p50) due to the upregulation of IRF2BP2, potentially affecting specific gene expressions involved in immune regulation<em>.</em></p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110326"},"PeriodicalIF":4.5,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylation of Interleukin-1 receptor-associated kinase-3 and the risk of multiple sclerosis relapse/activity","authors":"Mona M. Watany ,&nbsp;Marwa M. Elhosary ,&nbsp;Hemat E. El-Horany ,&nbsp;Mahmoud E. El-Horany","doi":"10.1016/j.clim.2024.110327","DOIUrl":"10.1016/j.clim.2024.110327","url":null,"abstract":"<div><p>This study retrospectively investigated the impact of interleukin-1 receptor-associated kinase-3 (IRAK-3/IRAK-M) silencing by methylation on the likelihood of multiple sclerosis (MS) activity. This cross-sectional study included 90 patients with MS: 45 with active disease (Group 1), 45 in remission (Group 2), and 45 healthy controls. The study included quantitation of IRAK-3 methylation index (MI%), IRAK-3 mRNA, and myeloid differentiation factor88 (MyD88) and assessment of NF-κB activity.</p><p>IRAK-3 MI% was significantly higher in group 1 compared to group 2, accompanied by lower IRAK-3 mRNA expression, elevated circulating MyD88, and increased NF-κB activity. IRAK-3 MI% correlated negatively with its transcript and positively with MyD88 and NF-κB activity. A logistic regression model was created to predict active demyelination. The C-index was 0.924, which indicates a very strong prediction model. Within the limitations of current work, IRAK-3 methylation level seems to be a promising candidate biomarker for identifying MS patients at risk of relapse.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110327"},"PeriodicalIF":4.5,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel insight into MDA-7/IL-24: A potent therapeutic target for autoimmune and inflammatory diseases","authors":"Kangni Feng,&nbsp;Jiemei Cen,&nbsp;Xiaoling Zou,&nbsp;Tiantuo Zhang","doi":"10.1016/j.clim.2024.110322","DOIUrl":"10.1016/j.clim.2024.110322","url":null,"abstract":"<div><p>Melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24 (IL-24) is a pleiotropic member of the IL-10 family of cytokines, and is involved in multiple biological processes, including cell proliferation, cell differentiation, tissue fibrosis, the inflammatory response, and antitumor activity. MDA-7/IL-24 can regulate epithelial integrity, homeostasis, mucosal immunity and host resistance to various pathogens by enhancing immune and inflammatory responses. Our recent study revealed the mechanism of MDA-7/IL-24 in promoting airway inflammation and airway remodeling through activating the JAK/STAT3 and ERK signaling pathways in bronchial epithelial cells. Herein, we summarize the cellular sources, inducers, target cells, signaling pathways, and biological effects of MDA-7/IL-24 in several allergic and autoimmune diseases. This review also synopsizes recent advances in clinical research targeting MDA-7/IL-24 or its receptors. Based on these advancements, we emphasize its potential as a target for immunotherapy and discuss the challenges of developing immunotherapeutic drugs targeting MDA-7/IL-24 or its receptors in autoimmune and inflammatory disorders.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110322"},"PeriodicalIF":4.5,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenic role and diagnostic utility of interferon-α in histiocytic necrotizing lymphadenitis","authors":"Shuya Kaneko ,&nbsp;Asami Shimbo ,&nbsp;Hitoshi Irabu ,&nbsp;Maho Hatano ,&nbsp;Kei Takasawa ,&nbsp;Takahiro Kamiya ,&nbsp;Keiji Akamine ,&nbsp;Takayuki Tanaka ,&nbsp;Toshinori Minato ,&nbsp;Makoto Ono ,&nbsp;Koji Yokoyama ,&nbsp;Atsuko Arisaka ,&nbsp;Takahiro Yasumi ,&nbsp;Kazuyuki Ueno ,&nbsp;Shuhei Fujita ,&nbsp;Yumi Tanaka ,&nbsp;Daisuke Hayashi ,&nbsp;Hiroki Nishikawa ,&nbsp;Yuji Fujita ,&nbsp;Yuki Yuza ,&nbsp;Masaki Shimizu","doi":"10.1016/j.clim.2024.110324","DOIUrl":"10.1016/j.clim.2024.110324","url":null,"abstract":"<div><h3>Purpose</h3><p>Histiocytic necrotizing lymphadenitis (HNL) is an inflammatory disease of unknown etiology clinically characterized by painful lymphadenopathy. This study aimed to investigate the role of interferon (IFN)-α in the pathogenesis of HNL and the clinical significance of serum IFN-α levels for the diagnosis and monitoring of HNL disease activity.</p></div><div><h3>Methods</h3><p>This study enrolled 47 patients with HNL and 43 patients with other inflammatory diseases that require HNL differentiation including malignant lymphoma (ML), bacterial lymphadenitis, and Kawasaki disease. Expression of IFN-stimulated genes (ISGs) and MX1 in the lymph nodes was measured by real-time quantitative reverse transcription polymerase chain reaction and immunofluorescence staining, respectively. Enzyme-linked immunosorbent assay was used to quantify serum cytokine levels. The results were compared with the clinical features and disease course of HNL.</p></div><div><h3>Results</h3><p>Patients with HNL had a significantly elevated ISG expression in the lymph nodes compared with those with ML. MX1 and CD123, a specific marker of plasmacytoid dendritic cells (pDCs), were colocalized. In patients with HNL, serum IFN-α levels were significantly elevated and positively correlated with disease activity. The serum IFN-α level cutoff value for differentiating HNL from other diseases was 11.5 pg/mL.</p></div><div><h3>Conclusion</h3><p>IFN-α overproduction from pDCs may play a critical role in HNL pathogenesis. The serum IFN-α level may be a valuable biomarker for the diagnosis and monitoring of disease activity in patients with HNL.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110324"},"PeriodicalIF":4.5,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aberrant innate immune profile associated with COVID-19 mortality in Pretoria, South Africa","authors":"Mieke A. van der Mescht ,&nbsp;Zelda de Beer ,&nbsp;Helen C. Steel ,&nbsp;Ronald Anderson ,&nbsp;Andries Masenge ,&nbsp;Penny L. Moore ,&nbsp;Paul Bastard ,&nbsp;Jean-Laurent Casanova ,&nbsp;Fareed Abdullah ,&nbsp;Veronica Ueckermann ,&nbsp;Theresa M. Rossouw","doi":"10.1016/j.clim.2024.110323","DOIUrl":"10.1016/j.clim.2024.110323","url":null,"abstract":"<div><p>The African continent reported the least number of COVID-19 cases and deaths of all the continents, although the exact reasons for this are still unclear. In addition, little is known about the immunological profiles associated with COVID-19 mortality in Africa. The present study compared clinical and immunological parameters, as well as treatment outcomes in patients admitted with COVID-19 in Pretoria, South Africa, to determine if these parameters correlated with mortality in this population. The in-hospital mortality rate for the cohort was 15.79%. The mortality rate in people living with HIV (PLWH) was 10.81% and 17.16% in people without HIV (<em>p</em> = 0.395). No differences in age (<em>p</em> = 0.099), gender (<em>p</em> = 0.127) or comorbidities were found between deceased patients and those who survived. All four of the PLWH who died had a CD4+ T-cell count &lt;200 cells/mm³, a significantly higher HIV viral load than those who survived (<em>p</em> = 0.009), and none were receiving antiretroviral therapy. Seven of 174 (4%) patients had evidence of auto-antibodies neutralizing Type 1 interferons (IFNs). Two of the them died, and their presence was significantly associated with mortality (<em>p</em> = 0.042). In the adjusted model, the only clinical parameters associated with mortality were: higher fraction of inspired oxygen (FiO2) (OR: 3.308, <em>p</em> = 0.011) indicating a greater need for oxygen, high creatinine (OR: 4.424, <em>p</em> = 0.001) and lower platelet counts (OR: 0.203, <em>p</em> = 0.009), possibly secondary to immunothrombosis. Overall, expression of the co-receptor CD86 (<em>p</em> = 0.021) on monocytes and percentages of CD8+ effector memory 2 T-cells (OR: 0.45, <em>p</em> = 0.027) was lower in deceased patients. Decreased CD86 expression impairs the development and survival of effector memory T-cells. Deceased patients had higher concentrations of RANTES (<em>p</em> = 0.003), eotaxin (p = 0.003) and interleukin (IL)-8 (<em>p</em> &lt; 0.001), all involved in the activation and recruitment of innate immune cells. They also had lower concentrations of transforming growth factor (TGF)-β1 (<em>p</em> = 0.40), indicating an impaired anti-inflammatory response. The immunological profile associated with COVID-19 mortality in South Africa points to the role of aberrate innate immune responses.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110323"},"PeriodicalIF":4.5,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624004327/pdfft?md5=1c5a69bb103d67dde6d8276584e7e5af&pid=1-s2.0-S1521661624004327-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A patient-based murine model recapitulates human STAT3 gain-of-function syndrome","authors":"Kornvalee Meesilpavikkai ,&nbsp;Zijun Zhou ,&nbsp;Kasiphak Kaikaew ,&nbsp;Suphattra Phakham ,&nbsp;Peter J. van der Spek ,&nbsp;Sigrid Swagemakers ,&nbsp;Deon J. Venter ,&nbsp;Maaike de Bie ,&nbsp;Benjamin Schrijver ,&nbsp;Christopher Schliehe ,&nbsp;Fabian Kaiser ,&nbsp;Virgil A.S.H. Dalm ,&nbsp;P. Martin van Hagen ,&nbsp;Nattiya Hirankarn ,&nbsp;Hanna IJspeert ,&nbsp;Willem A. Dik","doi":"10.1016/j.clim.2024.110312","DOIUrl":"10.1016/j.clim.2024.110312","url":null,"abstract":"<div><p>STAT3 gain-of-function (GOF) variants results in a heterogeneous clinical syndrome characterized by early onset immunodeficiency, multi-organ autoimmunity, and lymphoproliferation. While 191 documented cases with <em>STAT3</em> GOF variants have been reported, the impact of individual variants on immune regulation and the broad clinical spectrum remains unclear. We developed a <em>Stat3</em>^p.L387R mouse model, mirroring a variant identified in a family exhibiting common <em>STAT3</em> GOF symptoms, and rare phenotypes including pulmonary hypertension and retinal vasculitis. <em>In vitro</em> experiments revealed increased STAT3 phosphorylation, nuclear migration, and DNA binding of the variant. Our <em>Stat3</em>^p.L387R model displayed similar traits from previous <em>Stat3</em>^GOF strains, such as splenomegaly and lymphadenopathy. Notably, <em>Stat3</em>^p.L387R/+ mice exhibited heightened embryonic lethality compared to prior <em>Stat3</em>^GOF/+ models and ocular abnormalities were observed. This research underscores the variant-specific pathology in <em>Stat3</em>^p.L387R/+ mice, highlighting the ability to recapitulate human <em>STAT3</em> GOF syndrome in patient-specific transgenic murine models. Additionally, such models could facilitate tailored treatment development.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110312"},"PeriodicalIF":4.5,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Demyelinating strain of mouse hepatitis virus infection bridging innate and adaptive immune response in the induction of demyelination” [Clinical Immunology 170 (2016) 9–19]","authors":"Kaushiki Biswas ,&nbsp;Dhriti Chatterjee ,&nbsp;Sankar Addya ,&nbsp;Reas S. Khan ,&nbsp;Lawrence C. Kenyon ,&nbsp;Alexander Choe ,&nbsp;Randall J. Cohrs ,&nbsp;Kenneth S. Shindler ,&nbsp;Jayasri Das Sarma","doi":"10.1016/j.clim.2024.110307","DOIUrl":"10.1016/j.clim.2024.110307","url":null,"abstract":"","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110307"},"PeriodicalIF":4.5,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624004169/pdfft?md5=9216344411d05812a02ab0ea9de88334&pid=1-s2.0-S1521661624004169-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare Turner syndrome and lupus coexistence with insights from DNA methylation patterns","authors":"Gülşah Kavrul Kayaalp ,&nbsp;Desiré Casares-Marfil ,&nbsp;Sezgin Şahin ,&nbsp;Özgür Kasapçopur ,&nbsp;Betül Sözeri ,&nbsp;Nuray Aktay Ayaz ,&nbsp;Amr H. Sawalha","doi":"10.1016/j.clim.2024.110310","DOIUrl":"10.1016/j.clim.2024.110310","url":null,"abstract":"<div><p>Systemic lupus erythematosus (SLE or lupus) is a complex autoimmune disease that can affect multiple organs. While the exact disease etiology remains incompletely understood, there is a suggested influence of X-chromosome dosage in the pathogenesis of lupus. Here, we report a rare case of a female patient diagnosed with mosaic Turner syndrome and subsequently presenting with juvenile-onset SLE. DNA methylation patterns were analyzed in this patient and compared with age-matched female SLE controls, revealing higher methylation levels in interferon-regulated genes previously shown to be hypomethylated in SLE. These data provide a potential link between a gene-dose effect from the X-chromosome and the lupus-defining epigenotype. We hypothesize that the attenuated demethylation in interferon-regulated genes might provide a protective effect explaining the rarity of SLE in Turner syndrome.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110310"},"PeriodicalIF":4.5,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624004194/pdfft?md5=22bca384a0e1a66de9ab61fc2624456e&pid=1-s2.0-S1521661624004194-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenosine A2A receptor activation regulates the M1 macrophages activation to initiate innate and adaptive immunity in psoriasis","authors":"Yan Lu ,&nbsp;Wu Zhu ,&nbsp;Guan Xiong Zhang ,&nbsp;Jun Chen Chen ,&nbsp;Qiao Lin Wang ,&nbsp;Man Yun Mao ,&nbsp;Si Chun Deng ,&nbsp;Li Ping Jin ,&nbsp;Hong Liu ,&nbsp;Ye Hong Kuang","doi":"10.1016/j.clim.2024.110309","DOIUrl":"10.1016/j.clim.2024.110309","url":null,"abstract":"<div><p>Psoriasis is a common inflammatory systemic disease characterized by pro-inflammatory macrophages activation (M1 macrophage) infiltrated in the dermal layer. How M1 macrophage contributes to psoriasis remains unknown. In this study, we found that adenosine A2A receptor (A2AR) agonist CGS 21680 HCl alleviated the imiquimod (IMQ) and mouse IL-23 Protein (rmIL-23)-induced psoriasis inflammation through reducing infiltration of M1. Conversely, Adora2a deletion in mice exacerbated psoriasis-like phenotype. Mechanistically, A2AR activation inhibited M1 macrophage activation via the NF-κB-KRT16 pathway to reduce the secretion of CXCL10/11 and inhibit Th1/17 differentiation. Notably, the KRT16 expression was first found in M1 macrophage in our study, not only in keratinocytes (KCs). CXCL10/11 are first identified as primarily derived from macrophages and dendritic cells (DCs) rather than KCs in psoriasis using single cell RNA sequencing (scRNA-Seq). In total, the study emphasizes the importance of M1 as an innate immune cell in pathogenesis of psoriasis.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110309"},"PeriodicalIF":4.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}