title: Overexpression of RORγt Enhances Pulmonary Inflammation after Infection with Mycobacterium Avium.
abstract: Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial disease in humans. The role of Th17 immunity in the pathogenesis of intracellular bacteria, such as MAC, is not currently understood. Transcription factor RAR-related orphan receptor gamma t (RORγt) is known as the master regulator for Th17 cell development. Here, we investigated the role of RORγt in host responses against MAC infection. Wild-type (WT) mice and RORγt-overexpressing mice were infected with MAC via intratracheal inoculation. Systemic MAC growth was not different between WT mice and RORγt-overexpressing mice. However, neutrophilic pulmonary inflammation following MAC infection was enhanced in RORγt-overexpressing mice compared with that in WT mice. The cytokine expression shifted toward a Th17 phenotype in the lungs of RORγt-overexpressing mice following MAC infection; the levels of IL-6 and IL-17 were significantly higher in the lung of these mice than in WT mice. In addition to the increase in IL-17 single-positive T cells, T cells producing both IL-17 and interferon-γ were elevated in the lung of RORγt-overexpressing mice following MAC infection. These findings suggest that RORγt overexpression-mediated Th17 bias contributes to local inflammation rather than systemic responses, by regulating neutrophil recruitment into the sites of infection during MAC infection.
authors.affiliation: Department of Respiratory Medicine, Division of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Matsuyama
authors.affiliation: Department of Respiratory Medicine, Division of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Department of Respiratory Medicine, Division of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Sakurai
authors.affiliation: Department of Respiratory Medicine, Division of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ano
authors.affiliation: Department of Respiratory Medicine, Division of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Morishima
authors.affiliation: Department of Nephrology, Division of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Keigyou
authors.initials: K
authors.lastname: Yoh
authors.affiliation: Department of Anatomy and Embryology, University of Tsukuba, Tsukuba, Japan.|International Institute for Integrative Sleep Medicine, Life Science Center, University of Tsukuba, Tsukuba, Japan.|Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Japan.|Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Clinical Research, National Hospital Organization, Higashinagoya National Hospital, Nagoya, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Department of Respiratory Medicine, Division of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hizawa
mesh_terms: D000818:Animals; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009162:Mycobacterium avium / Q000302:isolation & purification / Q000472:pathogenicity*; D015270:Mycobacterium avium-intracellulare Infection / Q000150:complications* / Q000382:microbiology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000502:physiology*; D011014:Pneumonia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D057132:Nuclear Receptor Subfamily 1, Group F, Member 3