IL-27 Derived From Macrophages Facilitates IL-15 Production and T Cell Maintenance Following Allergic Hypersensitivity Responses

Autor: Jutamas Suwanpradid, Min Jin Lee, Peter Hoang, Jeffery Kwock, Lauren P. Floyd, Jeffrey S. Smith, Zhinan Yin, Amber R. Atwater, Sudarshan Rajagopal, Ross M. Kedl, David L. Corcoran, Jennifer Y. Zhang, Amanda S. MacLeod
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Frontiers in Immunology, Vol 12 (2021)
Druh dokumentu: article
ISSN: 1664-3224
DOI: 10.3389/fimmu.2021.713304
Popis: Crosstalk between T cells, dendritic cells, and macrophages in temporal leukocyte clusters within barrier tissues provides a new concept for T cell activation in the skin. Activated T cells from these leukocyte clusters play critical roles in the efferent phase of allergic contact hypersensitivity (CHS). However, the cytokines driving maintenance and survival of pathogenic T cells during and following CHS remain mostly unknown. Upon epicutaneous allergen challenge, we here report that macrophages produce IL-27 which then induces IL-15 production from epidermal keratinocytes and dermal myeloid cells within leukocyte clusters. In agreement with the known role of IL-15 as a T cell survival factor and growth cytokine, this signaling axis enhances BCL2 and survival of skin T cells. Genetic depletion or pharmacological blockade of IL-27 in CHS mice leads to abrogated epidermal IL-15 production resulting in a decrease in BCL2 expression in T cells and a decline in dermal CD8+ T cells and T cell cluster numbers. These findings suggest that the IL-27 pathway is an important cytokine for regulating cutaneous T cell immunity.
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