Commensal myeloid crosstalk in neonatal skin regulates long-term cutaneous type 17 inflammation.
Commensal myeloid crosstalk in neonatal skin regulates long-term cutaneous type 17 inflammation.
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新生儿皮肤中的共生髓系串扰可调节长期皮肤 17 型炎症。
DOI：
10.1101/2023.09.29.560039
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Spitzer,Mat
中科院分区：
文献类型：
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作者：
Dhariwala,MiqdadO;DeRogatis,AndreaM;Okoro,JoyN;Weckel,Antonin;Tran,VictoriaM;Habrylo,Irek;Ojewumi,OluwasunmisolaT;Tammen,AllisonE;Leech,JohnM;Merana,GeilR;Carale,RicardoO;Barrere-Cain,Rio;Hiam-Galvez,KamirJ;Spitzer,Mat
早期生命屏障表面的微生物-免疫相互作用对健康与疾病的轨迹具有持久的影响。单核细胞、巨噬细胞和树突状细胞是屏障组织中的主要前哨细胞，但共生髓系串扰在组织发育过程中的显著作用尚不清楚。在这里，我们确认共生微生物促进了单核细胞在新生儿皮肤中的聚集。出生后这些单核细胞的短暂耗尽会导致皮肤T细胞产生IL-17A的增加，这种情况在成年后的CD4+T细胞中尤其持续，足以加剧炎性皮肤病理。新生儿皮肤单核细胞表达IL-1途径的负性调节因子。体内功能实验证实，T细胞中过多的IL-1R1信号是导致新生儿单核细胞枯竭小鼠17型失调反应的关键因素。因此，单核细胞进入新生儿皮肤的共生驱动波对于促进这一显著屏障组织的长期免疫动态平衡至关重要。
Early life microbe-immune interactions at barrier surfaces have lasting impacts on the trajectory towards health versus disease. Monocytes, macrophages and dendritic cells are primary sentinels in barrier tissues, yet the salient contributions of commensal-myeloid crosstalk during tissue development remain poorly understood. Here, we identify that commensal microbes facilitate accumulation of a population of monocytes in neonatal skin. Transient postnatal depletion of these monocytes resulted in heightened IL-17A production by skin T cells, which was particularly sustained among CD4+ T cells into adulthood and sufficient to exacerbate inflammatory skin pathologies. Neonatal skin monocytes were enriched in expression of negative regulators of the IL-1 pathway. Functional in vivo experiments confirmed a key role for excessive IL-1R1 signaling in T cells as contributing to the dysregulated type 17 response in neonatal monocyte-depleted mice. Thus, a commensal-driven wave of monocytes into neonatal skin critically facilitates long-term immune homeostasis in this prominent barrier tissue.