Immunology最新文献

{"title":"The Immune Rheostat: A Shared Regulatory Axis Linking Cancer Immune Evasion and Autoimmune Activation.","authors":"Sivasangari Balakrishnan, Karthi Muthuswamy","doi":"10.1111/imm.70198","DOIUrl":"https://doi.org/10.1111/imm.70198","url":null,"abstract":"<p><p>Cancer and autoimmune diseases are traditionally regarded as distinct clinical entities, yet growing evidence indicates that both arise from dysregulation of shared immune-regulatory pathways coordinating immune activation, peripheral tolerance and tissue homeostasis. Rather than acting as independent processes, immune checkpoint signalling, T-cell functional integrity, regulatory T-cell (Treg) stability, cytokine and myeloid-cell polarization, and spatial immune organization form interconnected circuits that determine the quality, magnitude, and persistence of immune responses. The direction and extent of perturbation within these pathways, rather than simple activation or inhibition, determines whether immune responses promote tumour evasion or autoimmunity. Clinical experience with immune checkpoint inhibitors provides compelling evidence for this shared biology: blockade of PD-1 or CTLA-4 restores antitumor immunity but frequently disrupts peripheral tolerance, producing immune-related adverse events that closely resemble spontaneous autoimmune disease, showing checkpoints function within a broader network balancing protective immunity with self-tolerance. In this review, we propose the immune rheostat as an integrative framework unifying these shared mechanisms across cancer and autoimmune disease. We examine checkpoint co-signalling, T-cell exhaustion, Treg epigenetic stability, cytokine/myeloid networks, spatial architecture, and biomarker signatures across the disease spectrum, illustrated through a lupus nephritis model in which restoring follicular regulatory (Tfr)-helper (Tfh) T-cell balance demonstrates how coordinated pathway rewiring restores homeostasis. This review offers a unified framework for shared immune regulation, proposes layer-specific therapeutic strategies and a matched, non-checkpoint-restricted biomarker panel for tracking patients along the rheostat, and situates this framework against related single-disease and checkpoint-centric models.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900405","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":"The Transcription Factor EGR2 Plays a Central Role in the Expansion and Function of TCRαβ\u0000 +\u0000 CD4\u0000 −\u0000 CD8\u0000 − Double Negative T Cells in lpr Lupus Mice","authors":"Rujuan Dai,&nbsp;Zhuang Wang,&nbsp;Bettina Heid,&nbsp;Christopher M. Reilly,&nbsp;S. Ansar Ahmed","doi":"10.1111/imm.70162","DOIUrl":"10.1111/imm.70162","url":null,"abstract":"<p>TCRαβ⁺CD4⁻CD8⁻ double negative T (TCRβ⁺DNT) cells are highly accumulated in human and murine lupus, although the origin and function of TCRβ⁺DNT cells remains largely elusive and controversy. Remarkably, conditional deletion of <i>Egr2</i> in lymphocytes significantly reduced TCRβ⁺NK1.1⁻ DNT cells, the dominant DNT type in B6/<i>lpr</i> mice. TCRβ⁺DNT cells of B6/<i>lpr</i> mice surprisingly had a lower expression of IFNγ, IL-17, and IL-10 compared to normal B6 mice, which was likely due to high CD138 expression in the TCRβ⁺DNT cells of B6/<i>lpr</i> mice. Conditionally deleting <i>Egr2</i> in B6/<i>lpr</i> mice increased IFNγ and IL-10, but not IL-17 in TCRβ⁺DNT cells. <i>Egr2</i> deletion suppressed IL-17 expression in TCRγδ⁺DNT cells, the major IL-17-expressing DNT cells in B6/<i>lpr</i> mice. The scRNA-seq analysis of DNT cells from <i>Egr2</i>\u0000 ^{\u0000 <i>−</i>/−}B6/<i>lpr</i> (CD2-Cre<i>Egr2</i>\u0000 ^{\u0000 <i>−</i>/−}B6/<i>lpr</i>, EK) and control <i>Egr2</i>\u0000 ^{\u0000 <i>fl/fl</i>\u0000}B6/<i>lpr</i> (EF) mice revealed a striking segregation of DNT clusters with distinct transcriptional profiles, identified as EK_dominant and EF_dominant DNT clusters. <i>Egr2</i> deletion in B6/<i>lpr</i> mice seemingly normalised Helios, Ly6C, and Ly6A/E expression to levels similar to B6 mice, implying that inhibition of EGR2 can effectively correct the abnormalities in DNT cells of B6/<i>lpr</i> mice. Further, we found that conditional <i>Egr2</i> deletion reduced TCRβ⁺DN thymocytes in B6/<i>lpr</i> mice and suppressed DNT-cell generation from in vitro cultured splenic CD8⁺ T cells, suggesting that EGR2 might promote TCRβ⁺DNT cells in <i>lpr</i> mice at both the thymic and peripheral stages. Together, this study is the first to reveal a critical role of EGR2 in regulating the expansion, heterogeneity, and function of TCRβ⁺DNT cells in lupus mice.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"179 2","pages":"224-235"},"PeriodicalIF":5.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.70162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294893","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":"Characterisation of HIV-1 Gag Cytotoxic T-Lymphocyte Epitopes in the Southern African Region—A Systematic Review","authors":"Tumelo L. Fortuin,&nbsp;Paballo Nkone,&nbsp;Shayne Loubser,&nbsp;Caroline T. Tiemessen,&nbsp;Simnikiwe H. Mayaphi","doi":"10.1111/imm.70156","DOIUrl":"10.1111/imm.70156","url":null,"abstract":"<p>During early HIV-1 infection, robust Cytotoxic T-lymphocyte (CTL) responses are mostly targeted at immunodominant Gag p24 epitopes to reduce HIV-1 viraemia to a set-point. The aim of this study was to review the current body of knowledge on HIV-1 Gag CTL epitopes in the southern African region where subtype C is prevalent. Peer-reviewed records were obtained from three databases: PubMed Central, Web of Science Core Collection, and Scopus, using the following search terms: HIV subtype C Gag epitopes, and HIV clade C Gag epitopes. The search results were restricted to countries within the southern African region, and only data published in English and between the years 2000–2025 were considered for this review. The search from the three databases produced a total of 2103 peer-reviewed records, and 49 records were included in the review. The majority of studies (58.44%) were conducted in South Africa, followed by Botswana (15.58%), Zambia (10.39%), Malawi (7.79%), Zimbabwe (6.49%) and Angola (1.30%). There were no studies identified from other southern African countries. A total of 60 Gag CTL epitopes were identified, of which 17 (28.33%) were located within the matrix protein (p17), 33 (55.00%) within the capsid protein (p24), and 4 (6.67%) within the Gag polyprotein (p2p7p1p6). The commonly detected immunodominant epitopes were mostly located within the Gag p24 protein; and included TPQDLNTML (TL9, Gag p24 48–56) and TSTLQEQIGW (TW10, Gag p24 108–117) present at 16.00% and 13.3%, respectively. The proportion of HLA-A, B and C allotypes in this systematic review were 18%, 78%, and 4%, respectively. The more common HLA-B allotypes that restrict immunodominant Gag epitopes and facilitate better control of HIV-1 were HLA-B*57, -B*58:01, -B*42:01 and -B*81:01. This systematic review has provided important insights into the description of immunodominant Gag epitopes and HLA-I alleles that contribute to the control of HIV-1 viraemia in the southern African region. It has also exposed that some CTL epitopes identified in the southern African studies are not reported on the Los Alamos HIV database (LANL HIV database). This highlights a need to have this database updated with this information as it is used as a reference for epitopes. This review could provide insights into the design of an epitope-based HIV-1 vaccine that would also be effective in the southern African region.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"179 2","pages":"165-184"},"PeriodicalIF":5.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148137735","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":"Epigenetic Gene Networks Governing Immune State Transitions Across the Lifespan","authors":"Ola A. Al-Ewaidat,&nbsp;Moawiah M. Naffaa","doi":"10.1111/imm.70161","DOIUrl":"10.1111/imm.70161","url":null,"abstract":"<p>Immune function across development, tissue repair, aging, and disease depends not only on signaling pathways but also on epigenetic architectures that determine whether coordinated transcriptional programs can be accessed and resolved. Increasing evidence indicates that epigenetic gene networks regulate the accessibility and reversibility of semi-stable immune states, shaping plastic, homeostatic, reparative, and degenerative configurations. We propose the concept of epigenetic transition windows, defined as temporally and contextually restricted intervals during which epigenetic constraints are relaxed, permitting coordinated and reversible transitions between immune states. During development, these windows are broad and support immune tolerance and adaptive plasticity. In adulthood they become spatially and temporally restricted, preserving stability while enabling conditional adaptation. With aging, they progressively narrow, contributing to chronic inflammation, impaired repair, and increased vulnerability to neurodegeneration. Conversely, pathological persistence of regulatory permissiveness may underlie immune evasion and sustained plasticity in cancer. We outline operational genomic readouts for quantifying transition windows, including chromatin accessibility variance, enhancer switching dynamics, reversibility metrics, and cross-cell coordination indices, and derive experimentally testable predictions that distinguish this model from pathway-centric or damage-centric explanations. By reframing immune dysfunction as a failure of regulated state transition rather than excessive signaling alone, this framework integrates inflammaging, trained immunity, immune resolution failure, and tumor immune escape within a unified regulatory architecture and provides a systems-level perspective on immune adaptability across the lifespan.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"179 2","pages":"185-209"},"PeriodicalIF":5.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.70161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277389","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":"Immune Checkpoints in Leukaemia as Gatekeepers of Immuno-Modulation","authors":"Jeyrubini Ramesh,&nbsp;Kang Zi Khor,&nbsp;Maheswaran Solayappan,&nbsp;Thevendran Ramesh,&nbsp;Julia Joseph,&nbsp;Yee Yik Mot,&nbsp;Roshan Mascarenhas,&nbsp;Norashikin Zakaria,&nbsp;Norfarazieda Hassan,&nbsp;Adam Azlan,&nbsp;Emmanuel Jairaj Moses","doi":"10.1111/imm.70163","DOIUrl":"10.1111/imm.70163","url":null,"abstract":"<p>Immune evasion remains one of the key hallmarks in cancer survival by which tumours avoid immune system response. Mechanism of immune evasion involved modulation of immune related cytokines, modulation of tumour microenvironment and immune checkpoints. Intrinsic workings of these mechanisms lead to a network of ‘on’ and ‘off’ switches which could modulate immune activity. Interestingly in leukaemia, a complex network is involved as immune masking occurred concomitantly with leukaemogenesis within the same microenvironment, which makes immune evasion a more elusive hallmark for this disease. Dysregulation of these mechanisms not only facilitates disease persistence and progression but also contributes to resistance against conventional therapies. Therefore, understanding the role of leukaemic immune checkpoints is essential for identifying novel therapeutic targets and improving the efficacy of immunomodulatory treatment strategies. Here, we focus on the leukaemic immune checkpoints as these consist of crucial surface molecules, receptors, ligands, and immunosuppressive cells which interact within the tumour environment to enable leukaemia to elude immune response.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"179 2","pages":"236-257"},"PeriodicalIF":5.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.70163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307955","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":"Soluble Immune Checkpoints and Anti-HLA Antibodies in Kidney Transplant Recipients: Associations With Kidney Function","authors":"Cemil Pehlivanoğlu,&nbsp;Fırat Demircan,&nbsp;Başak Aru,&nbsp;Süheyla Apaydın,&nbsp;Abdullah Demir,&nbsp;Rabia Tığlı,&nbsp;Gürkan Tellioğlu,&nbsp;Ali Osman Gürol,&nbsp;Gülderen Yanıkkaya Demirel","doi":"10.1111/imm.70165","DOIUrl":"10.1111/imm.70165","url":null,"abstract":"<p>Kidney transplantation is the optimal treatment for end-stage renal disease. Soluble immune checkpoints (sICs) may serve as key immune regulators and potential biomarkers in transplantation. In this study, frozen serum samples from kidney transplant recipients (<i>n</i> = 30) at pre-transplantation (day 0) and post-transplantation (days 3 and 7), along with samples from healthy controls (HCs, <i>n</i> = 15), were analysed for sICs (sCD25, s4-1BB, sCD86, active TGF-β1, sCTLA-4, sPD-L1, sPD-1, sTIM-3, sLAG-3, galectin-9, sCD27, and sPD-L2) using a flow cytometry-based multiplex bead assay. To assess alloimmune sensitisation, anti-HLA panel-reactive antibody (PRA) levels were measured in transplant recipients. Kidney function was evaluated retrospectively by serum creatinine and estimated glomerular filtration rate (eGFR, CKD-EPI). All data were analysed to investigate their associations with kidney function. Pre-transplant patients had significantly higher serum levels of sCD25, sPD-L1, sTIM-3, Galectin-9, sCD27, and sPD-L2 compared to HCs. Post-transplant, sCD25, sPD-L1, sTIM-3, Galectin-9, sCD27, sPD-L2, and sCD86 showed significant temporal changes. Conversely, s4-1BB, sLAG-3, sCTLA-4, active TGF-β1, and sPD-1 levels showed no temporal changes and were comparable to HCs. Notably, PRA-positive patients exhibited higher sTIM-3 levels. Correlation and subgroup analyses based on eGFR revealed that higher levels sLAG-3 and sCTLA-4 levels were associated with better kidney function, while higher sCD25 and Galectin-9 levels were linked with poorer function. These findings suggest a link between sICs and renal function in the early post-transplant period, highlighting their potential as biomarkers and therapeutic targets. Future studies with larger cohorts are needed to evaluate their clinical utility in improving transplant outcomes.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"179 2","pages":"269-286"},"PeriodicalIF":5.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.70165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404624","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":"Comment on: Singh AK et al. From Radiation-Induced Immune Reprogramming to Globally Implementable Radio-Immunology","authors":"Rajeev Kumar Jha,&nbsp;M. Srikanth,&nbsp;M. Vijayasimha","doi":"10.1111/imm.70175","DOIUrl":"10.1111/imm.70175","url":null,"abstract":"","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"179 2","pages":"163-164"},"PeriodicalIF":5.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602456","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":"Epidermal Dominance of Metabolically Constrained Immune Niches Underpins Immune Activation Signatures and Clinical Severity in Psoriatic Disease","authors":"Caio Santos Bonilha","doi":"10.1111/imm.70164","DOIUrl":"10.1111/imm.70164","url":null,"abstract":"<div>\u0000 \u0000 <p>Psoriatic disease is characterised by persistent immune activation that is closely linked to tissue context and clinical severity. How immune metabolism is organised within inflamed skin and across systemic immune compartments remains incompletely elucidated. Here, spatial transcriptomics and CITE-seq datasets were analysed to characterise immune metabolic niche organisation across skin and circulation. Two metabolic constraint axes capturing oxygen redox and nutrient limitation were used to define metabolically constrained and permissive immune niches within leukocyte-rich tissue regions and circulating immune lineages. Psoriatic lesions exhibited a pronounced shift towards metabolically constrained immune niches that distinguished psoriasis from atopic dermatitis. This imbalance showed strong spatial organisation, with dominance within the epidermis and close alignment with immune activation programmes. Epidermal metabolic organisation scaled with clinical severity and was accompanied by increased immune activation in severely affected tissue, while dermal organisation remained comparatively stable. Extending these observations to circulation, immune metabolic states were further skewed towards constraint in psoriatic patients with joint involvement, consistent with higher systemic inflammatory burden, with prominent effects observed in CD4 T cells. Together, these findings identify immune metabolic niche organisation as a spatially and systemically structured feature of psoriatic disease that links tissue architecture, immune activation and clinical severity.</p>\u0000 </div>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"179 2","pages":"258-268"},"PeriodicalIF":5.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360614","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":"IL-6/IL-6R-Mediated Mechanisms in Lung Cancer: From Pathogenesis to Potential Therapeutic Targets","authors":"Qamar Abuhassan,&nbsp;Hamzeh J. Al-Ameer,&nbsp;S. Renuka Jyothi,&nbsp;Priya Priyadarshini Nayak,&nbsp;P. Prakash,&nbsp;Gunjan Mukherjee,&nbsp;Aashna Sinha,&nbsp;Ozoda Hazratkulova","doi":"10.1111/imm.70170","DOIUrl":"10.1111/imm.70170","url":null,"abstract":"<p>Despite significant advancements in the oncology field, lung cancer remains the leading cause of cancer-related mortality worldwide. A key contributor to the increased mortality rate is the resistance exhibited by cancer cells to standard anticancer treatments, particularly in advanced stages of the disease. Evidence indicates that chronic inflammation within the tumour microenvironment (TME) promotes tumorigenesis and contributes to resistance to immunotherapy, radiotherapy and chemotherapy. Notably, the overexpression of the cytokine interleukin-6 (IL-6) has been documented in various tumours, including lung cancer. Both tumour-associated fibroblasts (TAFs) and tumour cells constitute the predominant sources of secreted IL-6 within the TME. Various research has elucidated the role of IL-6 and its signalling pathways in facilitating therapeutic resistance, metastasis and tumour progression in lung cancer. Consequently, targeting IL-6 and/or its receptor, in conjunction with other effective anticancer treatments, represents an ideal therapeutic technique for lung cancer management. This review aims to synthesize recent evidence on the function of the IL-6/IL-6R signalling pathway in lung cancer, with a focus on its role in therapy resistance, prognosis and tumour progression, on the basis of clinical and preclinical studies.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"179 2","pages":"287-316"},"PeriodicalIF":5.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.70170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548811","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":"Thymic APC Networks Orchestrate T-Cell Selection: Mechanisms and Therapeutic Opportunities in Immune Disorders","authors":"Yuqi Luo,&nbsp;Wenqin Wang,&nbsp;Jun Yan","doi":"10.1111/imm.70160","DOIUrl":"10.1111/imm.70160","url":null,"abstract":"<p>The thymus is a primary lymphoid organ where antigen-presenting cells (APCs) orchestrate the development of a self-tolerant and functional T-cell repertoire. Herein, we elucidate the pivotal role of thymic selection defects in autoimmune pathogenesis and evaluate targeted therapeutic strategies for these mechanisms. This review synthesises recent advances in understanding how cortical thymic epithelial cells (cTECs), medullary thymic epithelial cells (mTECs), dendritic cells (DCs), and B cells collaboratively mediate positive and negative selection. cTECs drive positive selection through thymus-specific antigen processing machinery, including the β5t-containing thymoproteasome and cathepsin L, which generate self-peptide–MHC complexes with moderated affinity. mTECs broadly express tissue-restricted antigens (TRAs) under the control of AIRE, establishing a foundational self-antigen landscape for central tolerance. DCs execute efficient clonal deletion via cross-presentation and antigen transfer, while B cells contribute to tolerance against soluble antigens through BCR-mediated uptake. We further quantify the relative contributions of these APC subsets during thymic selection and discuss how defects in these processes underlie autoimmune diseases and immunodeficiencies. Finally, we highlight emerging therapeutic strategies that target thymic selection mechanisms, including AIRE modulation, tolerogenic DC vaccines, and thymic tissue engineering. These insights not only advance our understanding of T-cell development but also offer novel avenues for immune reprogramming in disease.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"179 2","pages":"210-223"},"PeriodicalIF":5.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307928","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}