Interleukin 7 signaling in dendritic cells regulates the homeostatic roliferation and niche size of CD4(+) T cells
Guimond, Martin and Veenstra, Rachelle G. and Grindler, David J. and Zhang, Hua and Cui, Yongzhi and Murphy, Ryan D. and Kim, Su Young and Na, Risu and Hennighausen, Lothar and Kurtuluş, Sema and Erman, Batu and Matzinger, Polly and Merchant, Melinda S. and Mackall, Crystal L. (2009) Interleukin 7 signaling in dendritic cells regulates the homeostatic roliferation and niche size of CD4(+) T cells. Nature Immunology, 10 (2). pp. 149-157. ISSN 1529-2908
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Official URL: http://dx.doi.org/10.1038/ni.1695
IL-7 has been proposed as a primary driver of homeostatic peripheral expansion (HPE) occurring in response to lymphopenia. We show here that systemic IL-7 levels rise during lymphopenia due to diminished IL-7 utilization, and that this milieu supports HPE of CD8+, but not CD4+ T cells. Rather, HPE of CD4+ T cells requires IL-7 production by Class II+ dendritic cells, which co-express IL7R! (IL7R!DCs). Elevated stroma derived IL-7 in lymphopenic hosts paradoxically diminishes IL-7 production and Class II expression by IL7R!DCs via an IL-7R!, "C, STAT5 dependent feedback loop, diminishing support for CD4 HPE. This paradigm establishes IL7R!DCs as primary regulators of the peripheral CD4+ niche and explains the longstanding observation that lymphopenic humans undergoing HPE replenish CD8+ but not CD4+ T cell pools.
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