Site-specific regulation of Th2 differentiation within lymph node microenvironments.

Autor:	Lyons-Cohen MR; Department of Immunology, School of Medicine, University of Washington, Seattle, WA, USA., Shamskhou EA; Department of Immunology, School of Medicine, University of Washington, Seattle, WA, USA., Gerner MY; Department of Immunology, School of Medicine, University of Washington, Seattle, WA, USA.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2024 Apr 01; Vol. 221 (4). Date of Electronic Publication: 2024 Mar 04.
DOI:	10.1084/jem.20231282
Abstrakt:	T helper 2 (Th2) responses protect against pathogens while also driving allergic inflammation, yet how large-scale Th2 responses are generated in tissue context remains unclear. Here, we used quantitative imaging to investigate early Th2 differentiation within lymph nodes (LNs) following cutaneous allergen administration. Contrary to current models, we observed extensive activation and "macro-clustering" of early Th2 cells with migratory type-2 dendritic cells (cDC2s), generating specialized Th2-promoting microenvironments. Macro-clustering was integrin-mediated and promoted localized cytokine exchange among T cells to reinforce differentiation, which contrasted the behavior during Th1 responses. Unexpectedly, formation of Th2 macro-clusters was dependent on the site of skin sensitization. Differences between sites were driven by divergent activation states of migratory cDC2 from different dermal tissues, with enhanced costimulatory molecule expression by cDC2 in Th2-generating LNs promoting prolonged T cell activation, macro-clustering, and cytokine sensing. Thus, the generation of dedicated Th2 priming microenvironments through enhanced costimulatory molecule signaling initiates Th2 responses in vivo and occurs in a skin site-specific manner. (© 2024 Lyons-Cohen et al.)
Databáze:	MEDLINE
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