Cabric Vanja, Brown Chrysothemis C
Immuno-Oncology, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, USA; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Immuno-Oncology, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, USA; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Medicine Graduate School of Medical Sciences, New York, NY, USA.
Curr Opin Immunol. 2025 Aug;95:102570. doi: 10.1016/j.coi.2025.102570. Epub 2025 May 26.
Our body's mucosal surfaces interface with the external environment and are potential sites of entry for pathogens as well as noxious substances. Yet, these barrier sites are also colonized with symbiotic microbes and are in contact with harmless environmental antigens. Different barrier epithelia harbor distinct microbial communities that shape both the epithelial layer and local immune cells that maintain tissue homeostasis and tolerance to symbiotic microbes. This seemingly paradoxical peaceful co-existence of immune cells and microbes has fascinated immunologists for decades: how does the immune system balance inflammatory and tolerogenic responses? The mechanisms underlying peripheral immune tolerance to harmless foreign antigens have been most widely studied within the intestine, where the immune system must establish and maintain tolerance to harmless food and commensal antigens. Dysregulated immune responses to these antigens are linked to several human diseases, including inflammatory bowel disease, celiac disease, and food allergy. Understanding the cellular and molecular cues that promote intestinal immune tolerance is key to the development of effective therapeutic strategies for these pathologies. Here, we review recent insights into mechanisms of intestinal tolerance with a focus on recently identified RORγt antigen-presenting cells.
我们身体的黏膜表面与外部环境相接触,是病原体以及有害物质的潜在侵入部位。然而,这些屏障部位也定植着共生微生物,并且与无害的环境抗原相接触。不同的屏障上皮细胞含有不同的微生物群落,这些群落塑造了上皮层以及维持组织稳态和对共生微生物耐受性的局部免疫细胞。免疫细胞与微生物这种看似矛盾的和平共存已经吸引免疫学家数十年:免疫系统是如何平衡炎症反应和耐受性反应的?对外源无害抗原的外周免疫耐受机制在肠道中得到了最广泛的研究,在肠道中,免疫系统必须建立并维持对无害食物和共生抗原的耐受性。对这些抗原的免疫反应失调与多种人类疾病相关,包括炎症性肠病、乳糜泻和食物过敏。了解促进肠道免疫耐受的细胞和分子线索是开发针对这些病症的有效治疗策略的关键。在这里,我们综述了肠道耐受机制的最新见解,重点关注最近发现的RORγt抗原呈递细胞。
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