Inhibition of B Lymphopoiesis by Adipocytes and IL-1-Producing Myeloid-Derived Suppressor Cells Journal Article

Authors: Kennedy, D. E.; Knight, K. L.
Article Title: Inhibition of B Lymphopoiesis by Adipocytes and IL-1-Producing Myeloid-Derived Suppressor Cells
Abstract: B lymphopoiesis declines with age, and this decline correlates with increased adipose tissue in the bone marrow (BM). Also, adipocyte-derived factors are known to inhibit B lymphopoiesis. Using cocultures of mouse BM cells with OP9 stromal cells, we found that adipocyte-conditioned medium induces the generation of CD11b+Gr1+ myeloid cells, which inhibit B cell development in vitro. Adipocyte-conditioned medium-induced CD11b+Gr1+ cells express Arg1 (arginase) and Nos2 (inducible NO synthase) and suppress CD4+ T cell proliferation, indicating that these cells are myeloid-derived suppressor cells (MDSCs). Blocking arginase and inducible NO synthase did not restore B lymphopoiesis, indicating that inhibition is not mediated by these molecules. Transwell and conditioned-medium experiments showed that MDSCs inhibit B lymphopoiesis via soluble factors, and by cytokine array we identified IL-1 as an important factor. Addition of anti-IL-1 Abs restored B lymphopoiesis in BM cultures containing MDSCs, showing that MDSC inhibition of B lymphopoiesis is mediated by IL-1. By treating hematopoietic precursors with IL-1, we found that multipotent progenitors are targets of IL-1. This study uncovers a novel function for MDSCs to inhibit B lymphopoiesis through IL-1. We suggest that inflammaging contributes to a decline of B lymphopoiesis in aged individuals, and furthermore, that MDSCs and IL-1 provide therapeutic targets for restoration of B lymphopoiesis in aged and obese individuals.
Journal Title: Journal of immunology (Baltimore, Md.: 1950)
Volume: 195
Issue: 6
ISSN: 1550-6606; 0022-1767
Publisher: by The American Association of Immunologists, Inc  
Date Published: 2015
Start Page: 2666
End Page: 2674
Language: ENG
Notes: LR: 20150814; CI: Copyright (c) 2015; JID: 2985117R; aheadofprint