Natural occurring IL-17 producing T cells regulate the initial phase of neutrophil mediated airway responses.
Effector Th17 cells are a major source of IL-17, a critical inflammatory cytokine in autoimmune diseases and in host defenses during bacterial infections. Recently, splenic lymphoid tissue inducer-like cells have been reported to be a source of T cell independent IL-17. In this study, we report that the immune system contains a unique set of natural occurring IL-17 producing cell, "natural" Th17 (nTh17), which are a memory-like T cell subset. The nTh17 cells can develop in the absence of the IL-6/STAT3 signaling axis required by inducible Th17 cells. The nTh17 cell population is distinct from conventional inducible Th17 cells, since nTh17 cells express substantial amounts of IL-17A (IL-17), but not IL-17F, under the control of the master regulator, RORgammat. The nTh17 cells simultaneously produce IFN-gamma. DO11.10 transgenic mice with a Rag(-/-) background (DO11.10 Rag(-/-)) lack nTh17 cells, and, following intranasal administration of OVA, IL-17-dependent neutrophil infiltration occurs in DO11.10 transgenic mice, but not in DO11.10 Rag(-/-) mice. The impaired neutrophil-dependent airway response is restored by adaptive transfer of nTh17 cells into DO11.10 Rag(-/-) mice. These results demonstrate that a novel T cell subset, nTh17, facilitates the early phase of Ag-induced airway responses and host defenses against pathogen invasion before the establishment of acquired immunity.
Tanaka
Shinya
S
Laboratory for Signal Network, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Tsurumi, Yokohama, Kanagawa, Japan.
Yoshimoto
Takayuki
T
Naka
Tetsuji
T
Nakae
Susumu
S
Iwakura
Yo-Ichi
Y
Cua
Daniel
D
Kubo
Masato
M
D000818:Animals; D018893:Bronchoalveolar Lavage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019070:Cell Lineage; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D020381:Interleukin-17; D007371:Interferon-gamma; D010047:Ovalbumin