Id2-, RORγt-, and LTβR-independent initiation of lymphoid organogenesis in ocular immunity

Author:

Nagatake Takahiro12,Fukuyama Satoshi1,Kim Dong-Young13,Goda Kaoru1,Igarashi Osamu1,Sato Shintaro1,Nochi Tomonori1,Sagara Hiroshi1,Yokota Yoshifumi4,Jetten Anton M.5,Kaisho Tsuneyasu6,Akira Shizuo7,Mimuro Hitomi1,Sasakawa Chihiro1,Fukui Yoshinori8,Fujihashi Kohtaro9,Akiyama Taishin1,Inoue Jun-ichiro1,Penninger Josef M.10,Kunisawa Jun111,Kiyono Hiroshi12911

Affiliation:

1. Division of Mucosal Immunology, Department of Microbiology and Immunology, Medical Proteomics Laboratory, Division of Bacterial Infection, Department of Microbiology and Immunology, and Division of Cellular and Molecular Biology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan

2. Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan

3. Department of Otorhinolaryngology, Seoul National University College of Medicine, Chongno-gu, Seoul 110-744, Korea

4. Department of Molecular Genetics, School of Medicine, University of Fukui, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan

5. Cell Biology Section, Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709

6. Laboratory for Host Defense, Research Center for Allergy and Immunology, Institute of Physical and Chemical Research, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan

7. Laboratory of Host Defense, World Premier International Research Center–Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan

8. Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan

9. Immunobiology Vaccine Center, Department of Pediatric Dentistry, The University of Alabama at Birmingham, Birmingham, AL 35294

10. Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria

11. Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan

Abstract

The eye is protected by the ocular immunosurveillance system. We show that tear duct–associated lymphoid tissue (TALT) is located in the mouse lacrimal sac and shares immunological characteristics with mucosa-associated lymphoid tissues (MALTs), including the presence of M cells and immunocompetent cells for antigen uptake and subsequent generation of mucosal immune responses against ocularly encountered antigens and bacteria such as Pseudomonas aeruginosa. Initiation of TALT genesis began postnatally; it occurred even in germ-free conditions and was independent of signaling through organogenesis regulators, including inhibitor of DNA binding/differentiation 2, retinoic acid–related orphan receptor γt, lymphotoxin (LT) α1β2–LTβR, and lymphoid chemokines (CCL19, CCL21, and CXCL13). Thus, TALT shares immunological features with MALT but has a distinct tissue genesis mechanism and plays a key role in ocular immunity.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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