Thermoneutral housing is associated with pathogenic upregulation of the IL-17 axis. (a) 6 week-old WT C57BL/6 male mice were housed at TS (22°C) or TN (30°C) conditions for 2 weeks prior to initiation of 8 weeks of HFD feeding. Upregulated gene expression pathway, and genes within pathway, determined by RNASeq analysis (n = 2 per group). (b–c) 6 week-old WT C57BL/6 male mice housed at TS (22°C; n = 3 per group) or TN (30°C; n = 4 per group) for 24 weeks and fed a HFD. (b) Percent of TCRβ+CD4+IL-17A+ hepatic infiltrating immune cells. (c) Percent of TCRβ+CD4+IL-17A+TNF+ hepatic infiltrating immune cells. (d–f) 6 week-old WT (n = 5 per group), IL-17RA−/− (n = 4 per group) and IL-17A−/− (n = 6 per group) male mice, all on C57BL/6 background, were housed at TN (30°C) conditions for 2 weeks prior to initiation of 24 weeks of HFD feeding. (d) Representative liver histology of WT (n = 5 per group), IL-17RA−/− (n = 4 per group) and IL-17A−/− (n = 6 per group) mice, by H&E staining at 20x and 40x magnification. Scale bars, 100μm (top) and 50μm (bottom). (e) NAFLD activity score. (f) serum ALT levels. (a) A single experiment. (b–f) A representative of 3 individual experiments. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. (b–c) Student’s t-test. (e–f) One way ANOVA with post hoc Tukey’s test.