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

Daisuke Kurotaki, Shigeyuki Kon, Kyeonghwa Bae, Koyu Ito, Yutaka Matsui, Yosuke Nakayama, Masashi Kanayama, Chiemi Kimura, Yoshinori Narita, Takashi Nishimura, Kazuya Iwabuchi, Matthias Mack, Nico Van Rooijen, Shimon Sakaguchi, Toshimitsu Uede, Junko Morimoto

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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 F4/80hiMac-1low MΦs residing in the red pulp showed different expression patterns of surface markers compared with F4/80 +Mac-1hi monocytes/MΦs. Studies with purified cell populations demonstrated that F4/80hiMac-1low MΦs regulated CD4+ T cell responses by producing soluble suppressive factors, including TGF-β and IL-10. Moreover, F4/80hiMac-1 low MFs induced the differentiation of naive CD4+ T cells into functional Foxp3+ regulatory T cells. Additionally, we found that the differentiation of F4/80hiMac-1low 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 F4/80hiMac-1low MΦs are a subpopulation of RPMs and regulate peripheral immune homeostasis.

Original languageEnglish
Pages (from-to)2229-2237
Number of pages9
JournalJournal of Immunology
Volume186
Issue number4
DOIs
Publication statusPublished - 2011 Feb 15
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kurotaki, D., Kon, S., Bae, K., Ito, K., Matsui, Y., Nakayama, Y., Kanayama, M., Kimura, C., Narita, Y., Nishimura, T., Iwabuchi, K., Mack, M., Van Rooijen, N., Sakaguchi, S., Uede, T., & Morimoto, J. (2011). CSF-1-dependent red pulp macrophages regulate CD4 T cell responses. Journal of Immunology, 186(4), 2229-2237. https://doi.org/10.4049/jimmunol.1001345