Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.713304
Keywords
contact hypersensitivity; human allergic contact dermatitis; IL-27; IL-15; dermal leukocyte cluster; BCL2; CD172a; STAT1
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Funding
- National Institutes of Health [R01AI139207]
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The crosstalk between T cells, dendritic cells, and macrophages in leukocyte clusters within barrier tissues provides a new concept for T cell activation in the skin. It was found that macrophages produce IL-27 which induces IL-15 production from other cells within leukocyte clusters, enhancing the survival of skin T cells. Blocking the IL-27 pathway in CHS mice led to decreased expression of the T cell survival gene BCL2, resulting in a decline in dermal CD8(+) T cells and T cell cluster numbers.
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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