Interleukin 7 signaling in dendritic cells regulates the homeostatic proliferation and niche size of CD4+ T cells

Martin Guimond, Rachelle G. Veenstra, David J. Grindler, Hua Zhang, Yongzhi Cui, Ryan D. Murphy, Su Young Kim, Risu Na, Lothar Hennighausen, Sema Kurtulus, Batu Erman, Polly Matzinger, Melinda S. Merchant, Crystal L. Mackall

Research output: Contribution to journalArticle

Abstract

Interleukin 7 (IL-7) and T cell antigen receptor signals have been proposed to be the main drivers of homeostatic T cell proliferation. However, it is not known why CD4+ T cells undergo less-efficient homeostatic proliferation than CD8+ T cells do. Here we show that systemic IL-7 concentrations increased during lymphopenia because of diminished use of IL-7 but that IL-7 signaling on IL-7 receptor-α-positive (IL-7Rα+) dendritic cells (DCs) in lymphopenic settings paradoxically diminished the homeostatic proliferation of CD4+ T cells. This effect was mediated at least in part by IL-7-mediated downregulation of the expression of major histocompatibility complex class II on IL-7Rα+ DCs. Our results indicate that IL-7Rα+ DCs are regulators of the peripheral CD4+ T cell niche and that IL-7 signals in DCs prevent uncontrolled CD4+ T cell population expansion in vivo.

Original languageEnglish (US)
Pages (from-to)149-157
Number of pages9
JournalNature Immunology
Volume10
Issue number2
DOIs
StatePublished - Jan 12 2009

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Guimond, M., Veenstra, R. G., Grindler, D. J., Zhang, H., Cui, Y., Murphy, R. D., Kim, S. Y., Na, R., Hennighausen, L., Kurtulus, S., Erman, B., Matzinger, P., Merchant, M. S., & Mackall, C. L. (2009). Interleukin 7 signaling in dendritic cells regulates the homeostatic proliferation and niche size of CD4+ T cells. Nature Immunology, 10(2), 149-157. https://doi.org/10.1038/ni.1695