An IL-9 fate reporter demonstrates the induction of an innate IL-9 response in lung inflammation

Abstract

Interleukin 9 (IL-9) is a cytokine implicated in lung inflammation, but its cellular origin and function remain unclear. Here we describe a reporter mouse strain designed to fate map cells that have activated IL-9. We show that during papain-induced lung inflammation IL-9 production was largely restricted to innate lymphoid cells (ILC). IL-9 production by ILC was dependent on IL-2 from adaptive immune cells and was rapidly lost in favor of other cytokines, such as IL-13 and IL-5. Blockade of IL-9 production via neutralizing antibodies substantially reduced IL-13 and IL-5, suggesting that ILC provide the missing link between the well-established functions of IL-9 on the regulation of TH2 cytokines and responses.

Immunity to gastrointestinal nematode infections

“…As with the role of IL-5 in promoting eosinophil responses, IL-9 acts mainly as a maturation factor for mucosal mast cells, [90][91][92] and is largely T cell derived, [93][94][95] although it can be secreted by ILC2, 96 as well as by mast cells themselves 97,98 that in turn promote enhanced secretion of IL-25, IL-33, and TSLP from epithelial cells. 99 As a result, T. muris and H. polygyrus expulsion are impaired in mast cell-deficient mice 99,100 as well as upon administration of neutralizing IL-9 antibodies, 101,102 although it should be noted that studies using mast celldeficient mice (c-kit mutants) suffer from possible confounding factors given the role for c-kit on many other cell types, and thus remain to be clarified.…”

Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease

“…Reprogramming between distinct CD4 + T cell subsets can be observed in human and mouse T cells under certain conditions in vitro [16][17][18][19] or in mice in vivo on transferring highly purified popu lations of cells [20][21][22][23][24][25] . By using lineage-tracing systems in mice, in which cells are engineered to express Cre recombinase under the control of transcriptional elements that regulate key polarization factors (such as cytokines or transcription factors) and a fluorescent protein reporter of Cre activity, endogenously polarized CD4 + T cells from many subsets have been found to change phenotype during their lifespan [26][27][28][29] . In humans, the combination of pheno typic analyses and sequencing of T cell receptors (TCRs), which act as unique barcodes for each T cell, has made it possible to investigate the phenotype of clonal descendants of single cells.…”

Type 2 Innate Lymphoid Cells Drive CD4+ Th2 Cell Responses

“…Experiments showed that IL-2, a predominantly T cell-derived cytokine, can influence ILC2 cytokine production (16), suggesting that ILC and Th cells might cooperate during the immune response. However, activation of ILC generally precedes that of Th cells, and whether and how ILCs influence Th cell activation and differentiation are unknown.…”