Natural occurring IL-17 producing T cells regulate the initial phase of neutrophil mediated airway responses

Shinya Tanaka, Takayuki Yoshimoto, Tetsuji Naka, Susumu Nakae, Yo Ichi Iwakura, Daniel Cua, Masato Kubo

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

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, RORγt. The nTh17 cells simultaneously produce IFN-γ. 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.

Original languageEnglish
Pages (from-to)7523-7530
Number of pages8
JournalJournal of Immunology
Volume183
Issue number11
DOIs
Publication statusPublished - Dec 1 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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