Regulatory T cells promote innate inflammation after skin barrier breach via TGF-β activation
| العنوان: | Regulatory T cells promote innate inflammation after skin barrier breach via TGF-β activation |
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| المؤلفون: | Ian C. Boothby, Joshua M. Moreau, Margaret M. Lowe, John Leech, Lokesh A. Kalekar, Michael Rosenblum, Jarish N. Cohen, Miqdad O. Dhariwala, Devi P. Boda, Courtney E. Macon, Victoire Gouirand, Tiffany C. Scharschmidt |
| المصدر: | Sci Immunol Science immunology, vol 6, iss 62 |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | T-Lymphocytes, 1.1 Normal biological development and functioning, Immunology, Integrin, Inflammation, chemical and pharmacologic phenomena, Mice, Transgenic, medicine.disease_cause, Inbred C57BL, Regenerative Medicine, T-Lymphocytes, Regulatory, Transgenic, Article, Autoimmunity, Mice, Mice, Congenic, Congenic, Underpinning research, Transforming Growth Factor beta, medicine, Innate, 2.1 Biological and endogenous factors, Animals, Aetiology, Skin, biology, 5.2 Cellular and gene therapies, integumentary system, business.industry, Regeneration (biology), Immunity, hemic and immune systems, General Medicine, Hair follicle, Regulatory, Epithelium, Immunity, Innate, Cell biology, Mice, Inbred C57BL, medicine.anatomical_structure, Emerging Infectious Diseases, Infectious Diseases, CXCL5, biology.protein, medicine.symptom, Development of treatments and therapeutic interventions, Wound healing, business |
| الوصف: | Regulatory T cells (Tregs) utilize multiple mechanisms to attenuate inflammation and prevent autoimmunity. Tregs residing in peripheral (i.e. nonlymphoid) tissues have specialized functions, specifically skin Tregs promote wound healing, suppress dermal fibrosis, facilitate epidermal regeneration and augment hair follicle cycling. Here, we demonstrated that skin Tregs were transcriptionally attuned to interact with their tissue environment through increased expression of integrin and TGF-β pathway genes that influence epithelial cell biology. We identified a molecular pathway where skin Tregs license keratinocytes to promote innate inflammation following skin barrier breach. Using a single cell discovery approach, we identified preferential expression of the integrin αvβ8 on skin Tregs. Upon skin injury, Tregs utilized this integrin to activate latent TGF-β which acted directly on epithelial cells to promote CXCL5 production and neutrophil recruitment. Induction of this circuit delayed epidermal regeneration but provided protection from Staphylococcus aureus infection across a compromised barrier. Thus, αvβ8 expressing Tregs in skin, somewhat paradoxical to their canonical immunosuppressive functions, facilitated inflammation acutely after loss of barrier integrity to promote host defense against infection. |
| وصف الملف: | application/pdf |
| تدمد: | 2470-9468 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a664ed6b93e5e8a7601ffe000f74f866 https://pubmed.ncbi.nlm.nih.gov/34452925 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a664ed6b93e5e8a7601ffe000f74f866 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 24709468 |
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