IL-17-producing innate lymphoid cells are restricted to mucosal tissues and are depleted in SIV-infected macaques

Innate lymphoid cells (ILCs) are an emerging subset of lymphocytes involved in surveillance against virally infected cells. Here, we show CD3(-)CD8(high) lymphocytes in macaque blood include major subsets of ILCs including natural killer (NK) cells expressing CD16, NKp46, and NKG2A, but also populations of ILCs in mucosal tissues having different properties. One ILC subset secreted interleukin (IL)-17 (ILC17), but these were restricted to mucosal tissues. Some mucosal ILC17 cells expressed classical NK-cell markers, but little NKG2A or NKG2D. Some ILC17 cells secreted IL-22 and tumor necrosis factor-alpha, but few produced interferon (IFN)-gamma or contained granzyme B. IL-17 production by ILCs was induced by IL-6, transforming growth factor-beta, and IL-23. Further, simian immunodeficiency virus (SIV) infection resulted in a significant loss of ILC17 cells, especially in the jejunum, which persisted throughout SIV infection. These findings indicate that ILC17 cells may be involved in innate mucosal immune responses, and their loss may contribute to loss of intestinal mucosal integrity and disease progression in human immunodeficiency virus (HIV)/SIV infection.