Felix Werner, Jens Wittner, Christian H K Lehmann, Mandy Wahlbuhl, Ida Allabauer, Adrian Hoffmann, Alexander Schnell, Tobias Krickau, Holger Hackstein, Barbara Dietel-Schor, James S Rush, Catherine H Regnier, Hans-Martin Jäck, Joachim Woelfle, Wolfgang Schuh, André Hoerning
{"title":"CD40 blockade hampers IgG class-switch while enhancing Granzyme B production by transitional B cells.","authors":"Felix Werner, Jens Wittner, Christian H K Lehmann, Mandy Wahlbuhl, Ida Allabauer, Adrian Hoffmann, Alexander Schnell, Tobias Krickau, Holger Hackstein, Barbara Dietel-Schor, James S Rush, Catherine H Regnier, Hans-Martin Jäck, Joachim Woelfle, Wolfgang Schuh, André Hoerning","doi":"10.1093/cei/uxaf044","DOIUrl":"https://doi.org/10.1093/cei/uxaf044","url":null,"abstract":"<p><p>CD40-CD40L interaction is crucial for the interplay between B and T cells and determines B cell fate. Here, we investigated the effects of CD40-CD40L inhibition on B cell subsets and cytokine production using the non-depleting monoclonal anti-CD40 antibody CFZ534. CFZ534 had no impact on B cell viability but inhibited TLR9-agonistic (CpG-ODN) CD40L- as well as CD40L-mediated proliferation. The plasmablast subset was reduced after stimulation with CpG-ODN+CD40L but this effect was completely restored by CFZ534-mediated CD40 blockade. IgG as well as IgM-secreting cells were significantly reduced in the presence of CFZ534 upon CD40L stimulation. CpG-ODN, but not CD40L, induced Granzyme B production in B cells after CD40-blockade and CpG-ODN/CD40L stimulation. Moreover, we found that IL-10 and Granzyme B were produced by separate B cell subsets. Hence, CD40-blockade mediated by CFZ534 increased Granzyme B production and decreased IL-10 production in CD24hiCD38hi B cells with a transitional phenotype and led to a significant decrease in the expression of the pro-inflammatory cytokines IL-6, IL-12p35 and IL-23p19 and TNFα in a B and CD4+ TH-cell co-culture system. Based on these pre-clinical results CD40 blockade by the Fc-silent, non-depleting monoclonal antibody CFZ534 exerts an anti-inflammatory effect on B cells including hampering the IgG class switch without affecting their viability. Graphical Abstract.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728353","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}
Aoife M O'Byrne, Cristoforo Grasso, Charlotte M de Winde, Aleksandra M Mikula, Catarina Gago da Graça, Johanna F Semmelink, Ester B M Remmerswaal, Janne W Bolt, Marleen G H van de Sande, Reina E Mebius, Lisa G M van Baarsen
{"title":"HLA-DR expressing lymph node fibroblasts maintain FoxP3+ regulatory T cells and are reduced in rheumatoid arthritis.","authors":"Aoife M O'Byrne, Cristoforo Grasso, Charlotte M de Winde, Aleksandra M Mikula, Catarina Gago da Graça, Johanna F Semmelink, Ester B M Remmerswaal, Janne W Bolt, Marleen G H van de Sande, Reina E Mebius, Lisa G M van Baarsen","doi":"10.1093/cei/uxaf042","DOIUrl":"https://doi.org/10.1093/cei/uxaf042","url":null,"abstract":"<p><strong>Introduction: </strong>Murine studies have demonstrated that lymph node fibroblasts can present self-antigens via major histocompatibility complex class II molecules, inducing functional regulatory T cells and contributing to peripheral tolerance.</p><p><strong>Methods: </strong>To investigate this phenomenon in humans, we developed an in vitro system co-culturing human lymph node fibroblasts with autologous CD4+ T cells.</p><p><strong>Results: </strong>Our results reveal that lymph node fibroblasts upregulate human leukocyte antigen-DR (HLA-DR) upon contact with CD4+ T cells and maintain FoxP3+ regulatory T cells. This maintenance is lost upon blockade of HLA-DR or interleukin-2, and regulatory T cells are lost in the absence of lymph node fibroblasts. Furthermore, we demonstrate that lymph node fibroblasts directly isolated from rheumatoid arthritis patients exhibit a significant reduction in the frequency of HLA-DR+ cells compared to those from individuals at risk of developing the disease.</p><p><strong>Conclusion: </strong>These findings highlight a crucial role for HLA-DR-expressing lymph node fibroblasts in maintaining peripheral tolerance within lymph nodes, a function that may be impaired in autoimmunity. Our study provides novel insights into the intricate cellular interactions within human lymph nodes and their potential implications in autoimmune disorders, opening new avenues for understanding and potentially treating these conditions.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526629","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":"Chronic Granulomatous disease: Lessons in Cell Biology From Monogenic Immunodeficiency.","authors":"Paige M Mortimer, Shuli Svetitsky, David C Thomas","doi":"10.1093/cei/uxaf031","DOIUrl":"https://doi.org/10.1093/cei/uxaf031","url":null,"abstract":"<p><p>Reactive oxygen species (ROS) are produced in immune cells by the phagocyte NADPH oxidase (NOX2) system that carries out coordinated transfer of electrons to molecular oxygen. The importance of the system in host defence and immunoregulation is underlined by chronic granulomatous disease (CGD), a severe monogenic immunodeficiency caused by mutations in genes encoding individual components of NOX2. CGD also leads to inflammatory manifestations due to the regulatory role of ROS in multiple signalling processes. We describe the system in detail, from its discovery to our current understanding of the oxidase. We also describe CGD and illustrate how recent insights into this disease shed light on physiology.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076347","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}
Rubiyat E Islam, Meaza Zewdie, Daniel Mussa, Yonas Abebe, Tom H M Ottenhoff, Kees L M C Franken, Fekadu Abebe, Liya Wassie
{"title":"The role of IgA and IgG in Mycobacterium tuberculosis infection: A cross-sectional study in Ethiopia.","authors":"Rubiyat E Islam, Meaza Zewdie, Daniel Mussa, Yonas Abebe, Tom H M Ottenhoff, Kees L M C Franken, Fekadu Abebe, Liya Wassie","doi":"10.1093/cei/uxaf001","DOIUrl":"https://doi.org/10.1093/cei/uxaf001","url":null,"abstract":"<p><strong>Introduction: </strong>Despite the high global prevalence of Mycobacterium tuberculosis (Mtb) infection in humans, most infected individuals achieve a stable immunological equilibrium, without showing clinical signs and symptoms of tuberculosis (TB). Although the role of antibodies in TB is assumed to be relatively small compared to cell-mediated immunity, their role in TB has been documented in a few recent studies.</p><p><strong>Methods: </strong>In this cross-sectional study, we quantitated antibody responses to Mtb antigens, lipoarabinomannan (LAM), and heparin-binding hemagglutinin adhesin (HBHA) by determining antigen-specific immunoglobulin A(IgA) and G(IgG) secretion levels using enzyme-linked immunosorbent assay (ELISA) in serum and saliva of pulmonary TB patients (PTB), their household contacts (HHC), and community controls (CC) (determined by QuantiFERON TB Gold assay QFT- test result).</p><p><strong>Results: </strong>The HBHA-specific IgA levels were significantly higher in both saliva and serum in HHC groups compared to PTB patients (P=0.013, P=0.023). Exposed contacts, who were QFT-negative had higher serum HBHA-specific IgA responses compared to PTB patients (P=0.04). QFT-negative HHC and QFT-positive CC showed higher HBHA and LAM-specific IgG responses (P=0.006, P=0.002, P=0.0009, P=0.006, respectively) than PTB patients. Generally, LAM and HBHA-specific IgA levels were significantly higher in saliva compared to serum (P<0.0001) in all study groups.</p><p><strong>Conclusion: </strong>Overall, the observed higher levels of IgA and IgG in controls, and exposed but QFT-negative contacts suggest a correlation with, and perhaps a role for these antibodies in preventing the development of active TB. The findings highlighted the potential involvement of saliva IgA in the immune response to Mtb, underscoring the relevance of mucosal immunity in TB infection.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413562","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":"Expression of Concern: Therapeutic effect of farnesylthiosalicylic acid on adjuvant-induced arthritis through suppressed release of inflammatory cytokines.","authors":"","doi":"10.1093/cei/uxae111","DOIUrl":"10.1093/cei/uxae111","url":null,"abstract":"","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806242","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}
Alexander Schnell, Carmen Aicher, Philipp A Schnegelsberg, Benedikt Schwarz, Hannah Schmidt, Ida Allabauer, Aline Rueckel, Adrian P Regensburger, Joachim Woelfle, André Hoerning
{"title":"Exhausted Lag-3+ CD4+ T cells are increased in pediatric Inflammatory Bowel Disease.","authors":"Alexander Schnell, Carmen Aicher, Philipp A Schnegelsberg, Benedikt Schwarz, Hannah Schmidt, Ida Allabauer, Aline Rueckel, Adrian P Regensburger, Joachim Woelfle, André Hoerning","doi":"10.1093/cei/uxae066","DOIUrl":"10.1093/cei/uxae066","url":null,"abstract":"<p><p>T cells are one of the main drivers of inflammatory bowel diseases (IBD). Infliximab (IFX) is used in the treatment of IBD as an anti-inflammatory drug to induce remission by neutralizing TNFα. We determined the individual chemokine/homing receptor and cytokine profile in pediatric IBD patients before and during IFX therapy to identify predictive biomarkers for therapy success. Peripheral blood CD4+ cells from pediatric patients with IBD were immunomagnetically isolated and either directly analyzed by FACS for cell distribution and chemokine/homing receptor expression or evaluated for cytokine production after in-vitro-stimulation. Twenty-one responders (RS) and 21 non-responders (NRS) were recruited. Before IFX therapy, flow cytometry revealed decreased percentages of naïve conventional T cells in pediatric IBD patients. The proportions of CD62-L+ T cells were decreased in both CD and UC therapy responders. The cytokine profile of T cells was highly altered in IBD patients compared to healthy controls (HC). During IFX therapy, the frequencies of conventional memory and regulatory memory T cells expanded in both cohorts. IFX response was marked by a decrease of α4β7+ and IFNγ+ memory T cells in both CD and UC. In contrast, frequencies of Lag-3+ T cells proved to be significantly increased in NRS. These observations were irrespective of the underlying disease. T cells of pediatric IBD patients display an activated and rather Th1/Th17-shifted phenotype. The increased expression of the checkpoint molecule Lag-3 on T cells of NRS resembles a more exhausted phenotype than in RS and HC which appeared to be a relevant predictive marker for therapy failure.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751239","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}
Katie J Smith, Zachary Lim, Sonja Vermeren, Veronique E Miron, Sarah Dimeloe, Donald J Davidson, Anna Williams, Emily Gwyer Findlay
{"title":"Proteomic analysis reveals dysregulation of peripheral blood neutrophils in patients with Multiple Sclerosis.","authors":"Katie J Smith, Zachary Lim, Sonja Vermeren, Veronique E Miron, Sarah Dimeloe, Donald J Davidson, Anna Williams, Emily Gwyer Findlay","doi":"10.1093/cei/uxae115","DOIUrl":"10.1093/cei/uxae115","url":null,"abstract":"<p><p>Multiple Sclerosis (MS) is a complex auto-inflammatory disease affecting the brain and spinal cord, which results in axonal de-myelination and symptoms including fatigue, pain, and difficulties with vision and mobility. The involvement of the immune system in the pathology of MS is well established, particularly the adaptive T cell response, and there has been a particular focus on the IL-17-producing subset of Th17 cells and their role in driving disease. However, the importance of innate immune cells has not been so well characterized. Here we focussed on neutrophils, which are innate immune cells and rapid responders to inflammation, and which have recently been linked to other chronic autoimmune conditions. Multiple strands of evidence in patients with MS and in mice with the experimental autoimmune encephalomyelitis MS model suggest neutrophils may play a role in driving MS inflammation. Here, we performed proteomic analysis on neutrophils from patients with MS and healthy donors, revealing striking differences. In particular, granule proteins were significantly more abundant in the MS neutrophils compared to the healthy controls, with a particular overabundance of proteins in primary and secondary granules. In addition, members of the MAVS signalling pathway were differently regulated compared to healthy donor cells. Finally, we find that MS neutrophils do not suppress T cell activation equivalently to healthy neutrophils, and in particular are unable to suppress expression of CD161 on the T cells, indicative of a suppression of Th17 differentiation. We propose that neutrophil dysregulation in MS may contribute to dysfunctional T cell responses.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001024","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":"Mimics and challenging presentations of DADA2.","authors":"Admir Öztürk, Lara Yagci, Serdal Ugurlu","doi":"10.1093/cei/uxaf017","DOIUrl":"10.1093/cei/uxaf017","url":null,"abstract":"<p><p>Deficiency of adenosine deaminase 2 (DADA2) has been a challenging diagnosis to make since it was first described in 2014. The disease represents a wide range of phenotypes. Therefore, it may present with various clinical patterns. Throughout the years, several difficult-to-diagnose cases of DADA2 were reported in the literature. Although several studies and reviews were published regarding different phenotypes and manifestations of DADA2, a review of challenging cases with diverse combinations of DADA2 manifestations was needed to integrate the knowledge from the literature into the clinical practice. Immunological, hematologic, autoinflammatory, and adult-onset polyarteritis-nodosa patterns were reported in the literature as cases challenging to diagnose. In this review, we aim to summarize the challenging case reports from the literature, provide an algorithmic approach for these kinds of presentations, and share our perspective and recommendations on the topic. Diagnosing DADA2 on time is a vital issue for preventing fatal and debilitating vascular events with anti-TNF-alpha therapy. Thus, early testing for DADA2 in suspected cases is recommended. Family history and genetic testing of the patient and the first-degree relatives are essential for accurate diagnosis. Thorough systemic examination and imaging might help detect clinically silent findings of vasculitis. Enzymatic activity of ADA2, when available, is also a key diagnostic tool that complements genetic testing and clinical evaluation.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673461","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":"Prospective analysis of the number and function of two T regulatory cell subsets in healthy individuals.","authors":"Erick Colunga-Bolaños, Lesly Doniz-Padilla, Marlen Vitales-Noyola, Larisa González-Baranda, Berenice Hernández-Castro, Perla Niño-Moreno, Diana P Portales-Pérez, Roberto González-Amaro","doi":"10.1093/cei/uxaf025","DOIUrl":"10.1093/cei/uxaf025","url":null,"abstract":"<p><strong>Introduction: </strong>T regulatory (Treg) cells play a crucial role in immune system homeostasis and in the pathogenesis of immune-mediated inflammatory diseases. Accordingly, numerous studies have examined the number and function of these lymphocytes in patients with different conditions as well as in healthy controls. The aim of this study was to analyze potential variations in the number and function of two Treg cell subsets in healthy adults over a 2-month period.</p><p><strong>Methods: </strong>In a pilot study, blood samples were collected from 20 healthy individuals on Days 0, 30, and 60, and the levels of natural Treg cells (CD4+CD25highFoxp3+) and CD69+ Treg cells (CD4+CD69+CD25-/+LAP+IL-10+Foxp3-) were analyzed by flow cytometry. In addition, the function of these regulatory cells was evaluated using an in vitro assay that measures the inhibition of activation of autologous T lymphocytes.</p><p><strong>Results: </strong>Although no significant differences were observed across the three serial measurements of the number or function of the Treg cells analyzed (P > 0.05 in both cases), a substantial proportion of individuals showed notable changes (either an increase or decrease) in these parameters during the study. These variations were not apparently associated with any factors affecting immune system homeostasis, including infections, medication use, or immunizations.</p><p><strong>Conclusion: </strong>Our findings suggest that significant fluctuations of causes to be determined occur in the levels and function of Treg cells in healthy individuals. This phenomenon should be considered in studies investigating immunoregulation in humans.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970931","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}
Aida Fiz-López, Ángel De Prado, Elisa Arribas-Rodríguez, Alejandro G Del Hierro, Carolina G de Castro, Sandra Izquierdo, Álvaro Martín-Muñoz, Daniel Corrales-Cruz, Sara Cuesta-Sancho, José A Garrote, Eduardo Arranz, Luis Fernández-Salazar, David Bernardo
{"title":"Restoration of the lamina propria duodenal immune infiltrate in gluten-free diet treated celiac patients despite persistent villous atrophy.","authors":"Aida Fiz-López, Ángel De Prado, Elisa Arribas-Rodríguez, Alejandro G Del Hierro, Carolina G de Castro, Sandra Izquierdo, Álvaro Martín-Muñoz, Daniel Corrales-Cruz, Sara Cuesta-Sancho, José A Garrote, Eduardo Arranz, Luis Fernández-Salazar, David Bernardo","doi":"10.1093/cei/uxaf058","DOIUrl":"10.1093/cei/uxaf058","url":null,"abstract":"<p><strong>Introduction: </strong>Although celiac disease (CD) current and only treatment is a life-long strict gluten-free diet (GFD), some patients suffer from persistent duodenal lesions despite years into the diet. Hence, we aimed to study the effect that the GFD elicits on the mucosal immune infiltrate from these patients.</p><p><strong>Method: </strong>To that end, duodenal biopsies were collected from non-celiac controls and CD patients, both at diagnosis and after at least one year into the GFD. The profile of duodenal intraepithelial lymphocytes (lymphogram) and the lamina propria immune infiltrate were determined by spectral cytometry.</p><p><strong>Results: </strong>At diagnosis, all CD patients had mucosal atrophy, a compatible lymphogram, and an expansion of lamina propria NK cells, innate lymphoid cells, B-cells, Treg and Tγδ cells, all of them expressing high levels of Fas, and Integrins α4 and β7. However, despite all GFD-treated patients had negative serology, 68.4% of them displayed persistent villous atrophy (Marsh score ≥ 3), while 73.3% had a compatible lymphogram. Nevertheless, despite such persistent atrophy, the lamina propria mucosal immune infiltrate was normalized in all GFD-treated patients. Besides, time on the GFD, but not the persistence of mucosal atrophy, correlated with an increased expression of gut-homing migration markers on lamina propria effector T-cells from these patients.</p><p><strong>Conclusion: </strong>Hence, we hereby have proved how the lamina propria immune infiltrate, as opposed to intraepithelial lymphocytes, is normalized in GFD-treated CD patients despite persistent villous atrophy, suggesting that the epithelial layer may be the driver of such paradoxical persistent mucosal inflammation.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022997","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}