Figure 5

JAK3 inhibition impairs human ILC proliferation and differentiation. (a–d) Effect of 48 h tofacitinib and (e,f) PF-06651600 culture on BrdU incorporation in expanded (a,b,e) iILC1 and (c,d,f) ILC3. Data show (a,c) representative flow plots, (b,d) quantification, and (e–f) representative dose–response curves. (g,h) Effect of 48 h tofacitinib culture on IFN-γ production in expanded human tonsillar iILC1. Data show (g) percentage of IFN-γ⁺ cells and (h) representative IFN-γ protein in supernatant of Donor 3 by CBA. (i) Percentage of IL-22⁺ ILC3 cells after IL-23 stimulation ex vivo in the presence of the indicated concentration of tofacitinib. (j) Representative IL-22 protein in supernatant of expanded human tonsillar ILC3 after 48 h of tofacitinib. (k) Percentage of IL-5⁺ mouse ILC2 after stimulation ex vivo in the presence of the indicated dose of tofacitinib. (l) Representative dose–response curve of IFN-γ protein in supernatant of cells treated for 24 h ex vivo with tofacitinib and PF-06651600. (m–o) Purified peripheral blood CD34⁺ cells were cultured in ILC-polarizing conditions for 14 days then incubated with the indicated concentration of tofacitinib and PF-06651600. (m) Representative flow plots of differentiated human ILC. (n) Quantification of percent CD56⁺NKp44⁺ cells among lineage negative lymphocytes. (o) Quantification of percent CD127⁺ cells among CD56⁺NKp44⁺ cells. Data represent (a–d,g–j) n=5 donors, (e,f,l) n=2 donors, (k) n=6 mice, or (m–o) n=3 donors. ^P<0.05, paired t-test. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, one-way ANOVA with Tukey’s multiple comparison test. ⁺P<0.05, ⁺⁺⁺P<0.001, ordinary one-way ANOVA. ANOVA, analysis of variance; ILC, innate lymphoid cell.

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