Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses

Immunity 30 (1):108-119, 2009

Harumichi Ishigame1, Shigeru Kakuta1, Takeshi Nagai2, Motohiko Kadoki1, Aya Nambu1, Yutaka Komiyama1, Noriyuki Fujikado1, Yuko Tanahashi1, Aoi Akitsu1, Hayato Kotaki1, Katsuko Sudo1,5, Susumu Nakae1, 3, Chihiro Sasakawa2, & Yoichiro Iwakura1, 4

1Center for Experimental Medicine, 2Department of Microbiology and Immunity, 3 Frontier Research Initiative, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan. 4Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Saitama 332-0012, Japan. 5Present address: Animal Research Center, Tokyo Medical University, 6-1-1 Shinjyuku, Shinjyuku-ku, Tokyo 160-8402, Japan.

IL-17A is a cytokine produced by T helper 17 (Th17) cells and plays important roles in the development of inflammatory diseases. Although IL-17F is highly homologous to IL-17A and binds the same receptor, the functional roles of this molecule remain largely unknown. Here, we demonstrated using Il17a-/-, Il17f-/-, and Il17a-/-Il17f-/- mice that IL-17F played only marginal roles, if at all, in the development of delayed-type and contact hypersensitivities, autoimmune encephalomyelitis, collagen-induced arthritis, and arthritis in Il1rn-/- mice. In contrast, both IL-17F and IL-17A were involved in host defense against mucoepithelial infection by Staphylococcus aureus and Citrobacter rodentium. IL-17A was produced mainly in T cells, whereas IL-17F was produced in T cells, innate immune cells, and epithelial cells. Although only IL-17A efficiently induced cytokines in macrophages, both cytokines activated epithelial innate immune responses. These observations indicate that IL-17A and IL-17F have overlapping yet distinct roles in host immune and defense mechanisms.

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