CSF-1-dependent red pulp macrophages regulate CD4 T cell responses.
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.
Division of Matrix Medicine, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Daisuke
D
Kurotaki
Shigeyuki
S
Kon
Kyeonghwa
K
Bae
Koyu
K
Ito
Yutaka
Y
Matsui
Yosuke
Y
Nakayama
Masashi
M
Kanayama
Chiemi
C
Kimura
Yoshinori
Y
Narita
Takashi
T
Nishimura
Kazuya
K
Iwabuchi
Matthias
M
Mack
Nico
N
van Rooijen
Shimon
S
Sakaguchi
Toshimitsu
T
Uede
Junko
J
Morimoto
D000595:Amino Acid Sequence; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D055879:Gene Knock-In Techniques; D006706:Homeostasis / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D013154:Spleen / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D000943:Antigens, Differentiation; D016177:Macrophage-1 Antigen; C036763:monocyte-macrophage differentiation antigen; D016173:Macrophage Colony-Stimulating Factor