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

First Author  Kurotaki D Year  2011
Journal  J Immunol Volume  186
Issue  4 Pages  2229-37
PubMed ID  21239712 Mgi Jnum  J:169161
Mgi Id  MGI:4939962 Doi  10.4049/jimmunol.1001345
Citation  Kurotaki D, et al. (2011) CSF-1-dependent red pulp macrophages regulate CD4 T cell responses. J Immunol 186(4):2229-37
abstractText  The balance between immune activation and suppression must be regulated to maintain immune homeostasis. Tissue macrophages (MPhis) constitute the major cellular subsets of APCs within the body; however, how and what types of resident MPhis are involved in the regulation of immune homeostasis in the peripheral lymphoid tissues are poorly understood. Splenic red pulp MPhi (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) MPhis residing in the red pulp showed different expression patterns of surface markers compared with F4/80(+)Mac-1(hi) monocytes/MPhis. Studies with purified cell populations demonstrated that F4/80(hi)Mac-1(low) MPhis regulated CD4(+) T cell responses by producing soluble suppressive factors, including TGF-beta and IL-10. Moreover, F4/80(hi)Mac-1(low) MPhis 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) MPhis was critically regulated by CSF-1, and in vitro-generated bone marrow-derived MPhis 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) MPhis are a subpopulation of RPMs and regulate peripheral immune homeostasis.
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