Non-classical Immunity Controls Microbiota Impact on Skin Immunity and Tissue Repair.,Cell

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Non-classical Immunity Controls Microbiota Impact on Skin Immunity and Tissue Repair.
Cell ( IF 45.5 ) Pub Date : 2018-Feb-08 , DOI: 10.1016/j.cell.2017.12.033
Jonathan L Linehan ₁ , Oliver J Harrison ₁ , Seong-Ji Han ₁ , Allyson L Byrd ₂ , Ivan Vujkovic-Cvijin ₁ , Alejandro V Villarino ₃ , Shurjo K Sen ₄ , Jahangheer Shaik ₅ , Margery Smelkinson ₆ , Samira Tamoutounour ₁ , Nicholas Collins ₁ , Nicolas Bouladoux ₇ , Amiran Dzutsev ₄ , Stephan P Rosshart ₈ , Jesse H Arbuckle ₉ , Chyung-Ru Wang ₁₀ , Thomas M Kristie ₉ , Barbara Rehermann ₈ , Giorgio Trinchieri ₄ , Jason M Brenchley ₁₁ , John J O'Shea ₃ , Yasmine Belkaid ₁

Affiliation

Mucosal Immunology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
Mucosal Immunology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD 20892, USA; Translational and Functional Genomics Branch, NHGRI, NIH, Bethesda, MD 20892, USA; Department of Bioinformatics, Boston University, Boston, MA 02215, USA.
Molecular Immunology and Inflammation Branch, NIAMS, NIH, Bethesda, MD 20892, USA.
Cancer and Inflammation Program, NCI, NIH, Bethesda, MD 20892, USA.
Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
Biological Imaging, Research Technology Branch, NIAID, NIH, Bethesda, MD 20892, USA.
Mucosal Immunology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD 20892, USA; NIAID Microbiome Program, NIH, Bethesda, MD 20892, USA.
Immunology Section, Liver Diseases Branch, NIDDK, NIH, Bethesda, MD 20892, USA.
Molecular Genetics Section, NIAID, NIH, Bethesda, MD 20892, USA.
Department of Microbiology and Immunology, Northwestern University, Chicago, IL 60611, USA.
Barrier Immunity Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD 20892, USA.

Mammalian barrier surfaces are constitutively colonized by numerous microorganisms. We explored how the microbiota was sensed by the immune system and the defining properties of such responses. Here, we show that a skin commensal can induce T cell responses in a manner that is restricted to non-classical MHC class I molecules. These responses are uncoupled from inflammation and highly distinct from pathogen-induced cells. Commensal-specific T cells express a defined gene signature that is characterized by expression of effector genes together with immunoregulatory and tissue-repair signatures. As such, non-classical MHCI-restricted commensal-specific immune responses not only promoted protection to pathogens, but also accelerated skin wound closure. Thus, the microbiota can induce a highly physiological and pleiotropic form of adaptive immunity that couples antimicrobial function with tissue repair. Our work also reveals that non-classical MHC class I molecules, an evolutionarily ancient arm of the immune system, can promote homeostatic immunity to the microbiota.

中文翻译：

非经典免疫控制微生物群对皮肤免疫和组织修复的影响。

哺乳动物屏障表面被许多微生物组成性地定殖。我们探索了免疫系统如何感测微生物群以及此类反应的定义特性。在这里，我们表明皮肤礼膜可以以仅限于非经典MHC I类分子的方式诱导T细胞反应。这些反应与炎症无关，与病原体诱导的细胞高度不同。共生特异性T细胞表达确定的基因特征，其特征在于效应基因的表达以及免疫调节和组织修复特征。因此，非经典的MHCI限制的共生特异性免疫反应不仅促进了对病原体的保护，而且还加速了皮肤伤口的闭合。因此，微生物群可以诱导高度生理性和多效性的适应性免疫，将抗菌功能与组织修复相结合。我们的工作还揭示了非经典的MHC I类分子，是免疫系统的一个进化古老的分支，可以促进对微生物群的稳态免疫。

更新日期：2018-01-18

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