IL-27 Derived From Macrophages Facilitates IL-15 Production and T Cell Maintenance Following Allergic Hypersensitivity Responses
Jutamas Suwanpradid, Min Jin Lee, Peter Hoang, J. Kwock, Lauren Floyd, Jeffrey S. Smith, Zhinan Yin, Amber Reck Atwater, Sudarshan Rajagopal, Ross M. Kedl, David L. Corcoran, Jennifer Zhang, Amanda S. MacLeod
Abstract
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.