A Brief History of IL-9

Abstract

IL-9 was first described in the late 1980s as a member of a growing number of cytokines that had pleiotropic functions in the immune system. Although many biological functions have been attributed to IL-9, it remains an understudied cytokine. A resurgence of interest in IL-9 has been spurred by recent work demonstrating a role for IL-9 in regulating inflammatory immunity and defining the transcription factors that activate the Il9 gene in cells that most efficiently produce IL-9. In this review, we summarize the characterization of IL-9 biological activities, highlight roles for the cytokine that are clearly defined, and outline questions regarding IL-9 functions that still require further exploration.

IL‐9 promotes the survival and function of human melanoma‐infiltrating CD4+CD8+ double‐positive T cells

“…It has been recently reported that IL-9 transcription in Th9 cells was regulated by the DNA-binding inhibitor Id3 [42]. Although we could not observe IL-9 production by our TILs expanded in vitro whatever the T-cell subpopulation tested (data not shown), IL-9 producing T cells associated with a Th9 phenotype were described in TILs from human melanoma lesions reinforcing the relevance of our data in vivo [43].While a large number of publications described diverse functions of IL-9 acting on a wide spectrum of hematopoietic and nonhematopoietic cell types [39], its effect on human TILs has not been documented yet. Previous studies, largely involving mouse models, have suggested that the common denominator of IL-9 function is to promote the survival of different cell types, including T cells [44] Furthermore, our results indicate that IL-9 treatment maintains, rather than induces, DP T-cell proliferation.…”

“…While a large number of publications described diverse functions of IL-9 acting on a wide spectrum of hematopoietic and nonhematopoietic cell types [39], its effect on human TILs has not been documented yet. Previous studies, largely involving mouse models, have suggested that the common denominator of IL-9 function is to promote the survival of different cell types, including T cells [44], mast cells [35], and eosinophils [45] as well as neurons [46], tumors [47], and epithelial cells [48].…”

“…Interest in IL-9 has been renewed recently owing to its expression by multiple T helper cell subsets and to its functions as both positive and negative regulator of immune responses in different pathologies [38]. IL-9 production was initially thought to be associated with Th2 cells until the recent identification of multiple IL-9 producing subsets including Th9, ILC2, Th17, and mast cells [39][40][41]. It has been recently reported that IL-9 transcription in Th9 cells was regulated by the DNA-binding inhibitor Id3 [42].…”

Suppression of systemic autoimmunity by the innate immune adaptor STING

“…S2G). Of note, IL-9 and IL-3 promote the proliferation and differentiation of hematopoietic stem cells into myeloid progenitor cells (19,20), and increased systemic levels of IL-9 and IL-3 correlate directly with the myeloid expansion seen in STING/lpr mice ( Fig. 4D).…”

Interleukin 10 rs1800872 T>G Polymorphism was Associated with an Increased Risk of Esophageal Cancer in a Chinese Population

“…IL9 is a pleiotropic cytokine in the T helper cell type 1 (Th1):Th2 pathway. Now, it was well known that a specialized subset termed Th9 cells selectively produce IL9 (Goswami et al, 2011). CDKN2A is a major susceptibility gene for cutaneous malignant melanoma (CMM).…”