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This Article Full Text (PDF) All Versions of this Article: jimmunol.0803828v1 183/11/7523    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Tanaka, S. Articles by Kubo, M. PubMed PubMed Citation Articles by Tanaka, S. Articles by Kubo, M.

Natural Occurring IL-17 Producing T Cells Regulate the Initial Phase of Neutrophil Mediated Airway Responses¹

Shinya Tanaka,^* Takayuki Yoshimoto, Tetsuji Naka, Susumu Nakae, Yo-ichi Iwakura, Daniel Cua,^¶ and Masato Kubo^2*

*Laboratory for Signal Network, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Tsurumi, Yokohama, Kanagawa, Japan; Intractable Immune System, Disease Research Center, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan; Laboratory for Immune Signal, National Institute of Biomedical Innovation, Ibaraki City, Osaka, Japan; Center for Experimental Medicine, The institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Japan; and ^¶Schering-Plough Biopharma (former DNAX Research), Palo Alto, CA 94304

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, RORt. The nTh17 cells simultaneously produce IFN-. 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.

Correspondence: ² Address correspondence and reprint requests to Dr. Masato Kubo, Laboratory for Signal Network, Research Center for Allergy and Immunology (RCAI), RIKEN Yokohama Institute, Suehiro-cho 1–7-22, Tsurumi, Yokohama, Kanagawa, Japan. E-mail address: raysolfc{at}rcai.riken.jp

¹ This study was supported by a Grant-in-Aid for Scientific Research (B) and a Grantin-Aid for Scientific Research on Priority Areas of the Ministry of Education, Culture, Sports, Science, and Technology (Japan) and the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO). Dr. S. Tanaka is a recipient of a fellowship from the Special Postdoctoral Researchers program of the RIKEN Yokohama Institute.