Fig. 5. CMTM4 regulates IL-17R-mediated inflammation and autoimmune pathology.
a, Flow cytometry analysis of intraperitoneal lavage from Cmtm4+/+ (WT) or Cmtm4−/− littermate mice that were intraperitoneally injected with IL-17A (500 ng) or PBS only for 4 h. CD45+ leukocyte subsets were gated as CD11b+F4/80+ residual macrophages, F4/80−CD11b+Ly6G+ neutrophils and F4/80−Ly6G−CD11b+Ly6C+ inflammatory monocytes. n = 12 (Cmtm4+/+ control), 13 (Cmtm4+/+ + IL-17A), 10 (Cmtm4−/− control) and 11 (Cmtm4−/− + IL-17A) in three independent experiments. Mean + s.e.m. Two-tailed Mann–Whitney test. NS, not significant. b, Flow cytometry analysis of IL-17RC surface expression in differentiated keratinocytes isolated from Cmtm4+/+ or Cmtm4−/− littermate mice. Mean + s.e.m. from five independent experiments. Two-tailed Mann–Whitney test. c, Analysis of experimental psoriasis disease progression in Cmtm4+/+ or Cmtm4−/− littermate mice treated with Aldara cream containing 5% IMQ on the shaved skin of back and ears daily for 5 consecutive days and monitored daily. n = 14 mice per group in three independent experiments. Mean ± s.e.m. score for erythema, scaling, dorsal skin thickness or combined cumulative score. Two-tailed Mann–Whitney test. d, Hematoxylin and eosin staining of sections of ear skin treated with Aldara for 4 days or the opposite ear in each mouse, which was left untreated, isolated from Cmtm4+/+ or Cmtm4−/− littermate mice. Scale bar, 100 µm, n = 6 mice per group. Mean ± s.e.m., two-tailed Mann–Whitney test. e, Real-time quantitative PCR analysis of the relative expression of DefB3, S100a8 and S100a9 transcripts in the back skin isolated from Cmtm4+/+ or Cmtm4−/− littermate mice treated or not with Aldara cream for 4 consecutive days. n = 4 for control groups, and 8 for IMQ-treated groups. Mean ± s.e.m., two-tailed Mann–Whitney test.