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

Abstract

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.

Changes in bone marrow innate lymphoid cell subsets in monoclonal gammopathy: target for IMiD therapy

“…The signals that lead to enrichment of these cells in the MGUS marrow remain to be clarified. In spite of small numbers, ILCs can significantly impact T-cell function by competing for cytokine niches 21 and therefore broadly impact immunity in the tumor bed. Alteration in ILC function in AMM patients suggests that changes in ILC function may also occur early in myelomagenesis.…”

Innate lymphoid cells, mediators of tissue homeostasis, adaptation and disease tolerance

“…While mice deprived of Vitamin A metabolites had reduced representation of ILC3, ILC2 were increased in number and activity. Increased IL‐7 availability in mice with reduced ILC3 numbers led to a competitive advantage of ILC2 and a type 2 tilt in immune responses resulting in increased immunity to helminth infections . These data link malnutrition to skewing of immune responses toward type 2 immunity.…”

Development of mucosal‐associated invariant T cells

“…Hence, it will be interesting to determine what factors these innate‐like T cells are competing for, and if other cell types are also involved in this interplay. For example, it was recently shown in mice that innate lymphoid cells compete with T cells for a limited supply of IL‐7 . Furthermore, IL‐7 is also required for the homeostasis and survival of mouse NKT17 cells .…”