{"id":387,"title":"IL-2-producing TFH cells sustain Treg cell homeostasis and immune tolerance in the gut","title_zh":"产生IL-2的滤泡辅助性T细胞维持肠道Treg细胞稳态与免疫耐受","url":"https://pubmed.ncbi.nlm.nih.gov/42907581","doi":"10.1038/s41590-026-02690-5","pmid":"42907581","journal":"Nat Immunol","kind":"paper","lang":"en","published_at":"2026-10-21T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Dave S","Bachus H","Santiago N","Meloun A","Smelkinson M","Foote JB","Hill T","Fucile C","Rosenberg AF","Ballesteros-Tato A"],"primary_topic":"repro-immunology","topics":[{"slug":"repro-immunology","score":7.0,"hits":["immune tolerance","treg"]},{"slug":"oocyte","score":1.0,"hits":["follicular"]},{"slug":"ethics-policy","score":1.0,"hits":["regulatory"]}],"topic_score":7.0,"preference_score":0.0,"preference_labels":[],"llm_score":52.0,"final_score":60.0,"score_dims":{"novelty":78,"rigor":80,"impact":45,"relevance":18,"translation":25},"recommend_reason":"机制新颖、实验体系扎实，但研究对象为肠道免疫耐受，与生殖、配子与胚胎的直接关联很弱，仅对理解生殖道黏膜免疫与免疫耐受有间接启发，故不列为必读。","keywords":["TFH细胞","IL-2","Treg细胞","肠道免疫耐受","肠道相关淋巴组织","结肠炎"],"selected":1,"story_id":346,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-top-journals","source_name":"PubMed · CNS/大子刊/四大医学刊（生殖相关）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"nat-immunol","journal_tier":"cns-sub","journal_if":27.7,"is_mock":false,"summary_zh":"研究在肠道相关淋巴组织（GALT）中鉴定出滤泡辅助性T（TFH）细胞的一项不依赖B细胞的新功能：TFH细胞在T细胞与B细胞交界区及滤泡间区产生IL-2，这种局部IL-2为维持GALT内调节性T（Treg）细胞稳态、抑制致病性效应T细胞扩增所必需。选择性缺失IL-2产生型TFH细胞的小鼠出现结肠炎及致死性多器官炎症，并伴GALT Treg反应受损与效应T细胞失控活化；广谱抗生素治疗可减轻肠道及肠外病变，提示对共生菌抗原的耐受丧失是疾病关键驱动因素。该研究定义了空间受限的TFH细胞来源IL-2微环境。","summary":"Follicular helper T (TFH) cells are well known for their role in supporting B cell responses. Here, we identify a critical B cell-independent function for TFH cells in sustaining regulatory T (Treg) cells within gut-associated lymphoid tissues (GALT). We demonstrate that TFH cells produce interleukin-2 (IL-2) at the T cell-B cell border and within interfollicular regions and that this localized IL-2 is required to maintain GALT Treg cell homeostasis and restrain the expansion of pathogenic effector T cells. Mice selectively lacking IL-2-producing TFH cells develop colitis and fatal multiorgan inflammation, driven by impaired GALT Treg cell responses and uncontrolled effector T cell activation. Broad-spectrum antibiotic treatment alleviates both intestinal and extraintestinal pathology, indicating that loss of tolerance to commensal-derived antigens is a key driver of disease. Together, these findings define a spatially restricted TFH cell-derived IL-2 niche critical for GALT Treg cell stability and uncover an unexpected immunoregulatory role for TFH cells in maintaining gastrointestinal tolerance beyond B cell help.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}