Innate type 2 immunity controls hair follicle commensalism by Demodex mites,Immunity

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Innate type 2 immunity controls hair follicle commensalism by Demodex mites
Immunity ( IF 25.5 ) Pub Date : 2022-08-30 , DOI: 10.1016/j.immuni.2022.08.001
Roberto R Ricardo-Gonzalez ₁ , Maya E Kotas ₂ , Claire E O'Leary ₂ , Katelyn Singh ₃ , William Damsky ₄ , Chang Liao ₂ , Elizabeth Arouge ₅ , Iliana Tenvooren ₆ , Diana M Marquez ₆ , Andrew W Schroeder ₂ , Jarish N Cohen ₇ , Marlys S Fassett ₈ , Jinwoo Lee ₂ , Scott G Daniel ₉ , Kyle Bittinger ₉ , Roberto Efraín Díaz ₁₀ , James S Fraser ₁₁ , Niwa Ali ₅ , K Mark Ansel ₁₂ , Matthew H Spitzer ₁₃ , Hong-Erh Liang ₂ , Richard M Locksley ₁₄

Affiliation

Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA.
Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
Department of Dermatology, Yale School of Medicine, New Haven, CT, USA; Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA.
Department of Otolaryngology and Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USA.
Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USA.
Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA; Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USA.
Department of Otolaryngology and Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA.
Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA.

Demodex mites are commensal parasites of hair follicles (HFs). Normally asymptomatic, inflammatory outgrowth of mites can accompany malnutrition, immune dysfunction, and aging, but mechanisms restricting Demodex outgrowth are not defined. Here, we show that control of mite HF colonization in mice required group 2 innate lymphoid cells (ILC2s), interleukin-13 (IL-13), and its receptor, IL-4Ra-IL-13Ra1. HF-associated ILC2s elaborated IL-13 that attenuated HFs and epithelial proliferation at anagen onset; in their absence, Demodex colonization led to increased epithelial proliferation and replacement of gene programs for repair by aberrant inflammation, leading to the loss of barrier function and HF exhaustion. Humans with rhinophymatous acne rosacea, an inflammatory condition associated with Demodex, had increased HF inflammation with decreased type 2 cytokines, consistent with the inverse relationship seen in mice. Our studies uncover a key role for skin ILC2s and IL-13, which comprise an immune checkpoint that sustains cutaneous integrity and restricts pathologic infestation by colonizing HF mites.

中文翻译：

先天 2 型免疫通过蠕形螨控制毛囊共生

蠕形螨是毛囊 (HF) 的共生寄生虫。通常无症状的螨虫炎症生长可能伴随营养不良、免疫功能障碍和衰老，但限制蠕形螨生长的机制尚不清楚。在这里，我们表明，控制螨虫 HF 在小鼠中的定植需要第 2 组先天淋巴细胞 (ILC2)、白细胞介素 13 (IL-13) 及其受体 IL-4Ra-IL-13Ra1。HF 相关的 ILC2 精心合成 IL-13，可在毛发生长初期减弱 HF 和上皮增殖；如果没有它们，蠕形螨定植导致上皮增殖增加，并替换异常炎症修复的基因程序，导致屏障功能丧失和心力衰竭。患有鼻赘痤疮红斑痤疮（一种与蠕形螨相关的炎症性疾病）的人，心力衰竭炎症增加，2 型细胞因子减少，与小鼠中观察到的反比关系一致。我们的研究揭示了皮肤 ILC2 和 IL-13 的关键作用，它们构成了维持皮肤完整性并通过定植 HF 螨来限制病理感染的免疫检查点。

更新日期：2022-08-30

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