Interleukin-7 Availability Is Maintained by a Hematopoietic Cytokine Sink Comprising Innate Lymphoid Cells and T Cells

Publication date: 18 July 2017
Source:Immunity, Volume 47, Issue 1
Author(s): Christopher E. Martin, Darina S. Spasova, Kwesi Frimpong-Boateng, Hee-Ok Kim, Minji Lee, Kwang Soon Kim, Charles D. Surh
Interleukin-7 (IL-7) availability determines the size and proliferative state of the resting T cell pool. However, the mechanisms that regulate steady-state IL-7 amounts are unclear. Using experimental lymphopenic mouse models and IL-7-induced homeostatic proliferation to measure IL-7 availability in vivo, we found that radioresistant cells were the source of IL-7 for both CD4⁺ and CD8⁺ T cells. Hematopoietic lineage cells, although irrelevant as a source of IL-7, were primarily responsible for limiting IL-7 availability via their expression of IL-7R. Unexpectedly, innate lymphoid cells were found to have a potent influence on IL-7 amounts in the primary and secondary lymphoid tissues. These results demonstrate that IL-7 homeostasis is achieved through consumption by multiple subsets of innate and adaptive immune cells.

Teaser

IL-7 availability for lymphocytes is thought to be set by the amount of IL-7 production by radioresistant cells, such as fibroblastic reticular cells, and consumption by IL-7R⁺ hematopoietic cells. Martin et al. confirm this finding and also find that ILCs can outcompete T cells for IL-7 by resisting downregulation of IL-7R through differential modulation of transcription factor FOXO1, which regulates IL-7R expression.


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