Fig. 4: Nod2 suppresses uveitis through a non-conventional cellular mechanism.

a–b CD4⁺ T cells from IRBP-immunized donor WT or Nod2^−/− mice were adoptively transferred into naïve WT recipients. a Clinical uveitis scores and incidence 20 days post-transfer. Data are from 6 independent experiments with n = 27 (WT) and 28 (Nod2^−/−) mice; *p = 0.0336. b Representative photos of WT recipients of WT or Nod2^−/− CD4⁺ T cells 20 days post-transfer. c IL-17 and IFN-γ were measured by ELISA following 18 h stimulation with IRBP_1–20 (20 µg/ml) of co-cultured APCs (isolated from naïve WT or Nod2^−/− mice) and CD4⁺ T cells (isolated from WT or Nod2^−/− immunized mice). Control APCs without the addition of T cells (“none”) were stimulated with IRBP. Data are combined from 4 independent experiments. For each experiment, APCs or T cell populations were isolated from n = 3 pooled mice/genotype; *p = 0.0286 for comparisons with both APC conditions. d–e Rag1^−/− or Nod2^−/−Rag1^−/−mice were reconstituted with WT CD4⁺ T cells and immunized with IRBP 24 h later. d Clinical uveitis was evaluated weekly. Data is combined from 3 independent experiments. For Rag1^−/− recipients n = 16 (7 days), 20 (14 days), 18 (21 and 28 days), 16 (35 days). For Nod2^−/−Rag1^−/− recipients n = 20 (7 days), 22 (14, 21, and 28 days), 20 (35 days). e Splenocytes were stimulated 18 h in vitro with IRBP_1–20 and IL-17 in culture supernatants was measured by ELISA. Data are combined from 3 independent experiments with n = 12 (Rag1^−/− media), 18 (Nod2^−/−Rag1^−/− media), 13 (Rag1^−/− IRBP), 15 (Nod2^−/−Rag1^−/− IRBP) mice; ***p = 0.0001. Data are mean ± SEM (a, d) with dots representing individual values (a) or box-whisker plots with median, 25–75th percentile and min–max range (c, e). Statistical differences between groups were calculated using unpaired, two tailed Student’s t-test (a), two-tailed Mann–Whitney U test (c, d, e). Source data are provided as a Source Data file.