CSF-1-dependent red pulp macrophages regulate CD4 T cell responses

• Published in: The Journal of immunology (1950) 2011-02, Vol.186 (4), p.2229-2237
• Main Authors: Kurotaki, Daisuke, Kon, Shigeyuki, Bae, Kyeonghwa, Ito, Koyu, Matsui, Yutaka, Nakayama, Yosuke, Kanayama, Masashi, Kimura, Chiemi, Narita, Yoshinori, Nishimura, Takashi, Iwabuchi, Kazuya, Mack, Matthias, van Rooijen, Nico, Sakaguchi, Shimon, Uede, Toshimitsu, Morimoto, Junko
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antigens, Differentiation - biosynthesis; Bone Marrow Cells - cytology; Bone Marrow Cells - immunology; Bone Marrow Cells - metabolism; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cells, Cultured; Gene Knock-In Techniques; Homeostasis - immunology; Macrophage Colony-Stimulating Factor - physiology; Macrophage-1 Antigen - biosynthesis; Macrophages - cytology; Macrophages - immunology; Macrophages - metabolism; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Transgenic; Molecular Sequence Data; Spleen - cytology; Spleen - immunology; Spleen - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1001345

The balance between immune activation and suppression must be regulated to maintain immune homeostasis. Tissue macrophages (MΦs) constitute the major cellular subsets of APCs within the body; however, how and what types of resident MΦs are involved in the regulation of immune homeostasis in the peripheral lymphoid tissues are poorly understood. Splenic red pulp MΦ (RPMs) remove self-Ags, such as blood-borne particulates and aged erythrocytes, from the blood. Although many scattered T cells exist in the red pulp of the spleen, little attention has been given to how RPMs prevent harmful T cell immune responses against self-Ags. In this study, we found that murine splenic F4/80(hi)Mac-1(low) MΦs residing in the red pulp showed different expression patterns of surface markers compared with F4/80(+)Mac-1(hi) monocytes/MΦs. Studies with purified cell populations demonstrated that F4/80(hi)Mac-1(low) MΦs regulated CD4(+) T cell responses by producing soluble suppressive factors, including TGF-β and IL-10. Moreover, F4/80(hi)Mac-1(low) MΦs induced the differentiation of naive CD4(+) T cells into functional Foxp3(+) regulatory T cells. Additionally, we found that the differentiation of F4/80(hi)Mac-1(low) MΦs was critically regulated by CSF-1, and in vitro-generated bone marrow-derived MΦs induced by CSF-1 suppressed CD4(+) T cell responses and induced the generation of Foxp3(+) regulatory T cells in vivo. These results suggested that splenic CSF-1-dependent F4/80(hi)Mac-1(low) MΦs are a subpopulation of RPMs and regulate peripheral immune homeostasis.