Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses.
Interleukin-17A (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 with 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.
Ishigame
Harumichi
H
Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Kakuta
Shigeru
S
Nagai
Takeshi
T
Kadoki
Motohiko
M
Nambu
Aya
A
Komiyama
Yutaka
Y
Fujikado
Noriyuki
N
Tanahashi
Yuko
Y
Akitsu
Aoi
A
Kotaki
Hayato
H
Sudo
Katsuko
K
Nakae
Susumu
S
Sasakawa
Chihiro
C
Iwakura
Yoichiro
Y
D000818:Animals; D001168:Arthritis / Q000235:genetics / Q000276:immunology*; D001424:Bacterial Infections / Q000276:immunology* / Q000517:prevention & control; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology*; D020381:Interleukin-17 / Q000145:classification* / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout
D016207:Cytokines; D020381:Interleukin-17