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. 2018 May 24;9:1139. doi: 10.3389/fimmu.2018.01139

Figure 1.

Figure 1

Complex role of IL-9-secreting Th9 cells in inflammatory bowel disease (IBD). Interleukin-9, a pleiotropic cytokine, is known to play dichotomous role in IBD. IL-9 secretion by Th9 cells disrupts intestinal barrier permeability resulting in the entry of innocuous antigens into the gut mucosa. This leads to antigen presentation by the dendritic cells to naïve CD4+ T cells culminating in T helper differentiation. Several cytokines are known to promote Th9 cell differentiation. IL-33 and IL-36 play a key role in Th9 cell proliferation in the gut mucosa culminating in aggravated colitis. IL-9 secreted by Th9 cells is also known to promote Th2-like responses culminating in the progression of ulcerative colitis (UC). However, IL-9 secreted by cells other than Th9 cells such as invariant natural killer T (iNKT) cells are known to dampen inflammatory responses rather than promoting them. Thus, anti-IL-9 antibody might not be the “magic bullet” to treat IBD. Instead, targeting the cytokines involved in Th9 cell expansion in the gut mucosa could be a possible strategy to maintain optimal Th9 cell development in the gut and thereby restrain Th9 cell-mediated UC.