Fig. 4. Tryptophan metabolism modulates autoimmune phenotypes in TC mice.

(A) Concentrations of tryptophan (Trp), kynurenine (Kyn) and serotonin (5HT) in feces and serum of 6-month-old B6 and TC mice are shown. (B) Shown is the quantitation of (F) fecal tryptophan, (S) serum kynurenine and the kynurenine/serotonin ratio in B6 and TC mice treated with antibiotic combination therapy (ampicillin, metronidazole, neomycin and vancomycin, AMNV) for 5 months or untreated. (C) Body weight loss of B6 and TC mice fed with tryptophan-deficient chow is shown (n = 5 per group). Shown are serum anti-dsDNA IgG concentrations in arbitrary units in TC mice fed chow with the indicated amount of tryptophan (%) after 4 months of treatment (D) and as a time-course during the treatment (E). (F) Correlation between serum kynurenine and anti-dsDNA IgG concentration in TC and B6 mice fed with chow containing 0.08 to 1.19 % tryptophan (n = 3 -- 5/group). (G) Renal pathology indicated as glomerulonephritis (GN) ranked scores from the lowest at 1 to the most severe at 24 in TC mice fed with variable amounts of tryptophan in their chow is shown. Frequencies of CD69⁺CD4⁺ cells (H), Ki67⁺ T_Act cells (I), Tfh cells (J) and Ki67⁺ Tfh cells (K) in spleen are shown. (L) Shown is proliferation of effector T cells in vitro in the presence of Treg cells isolated from TC mice fed chow with different amounts of tryptophan (0.08%, low, or1.19% high) n = 6/group). (M) Shown is the frequency of splenic germinal center B cells of TC mice fed chow with the indicated amounts of tryptophan (n = 5-10/group). Data are presented as means and SEM and are compared with Dunnetťs multiple comparison tests (panels A, B, D G-K), 2-way ANOVA (C and E), Pearson’s correlation (F and L), or Fisher Exact test (G). In panel D, medians are compared with the Mann-Whitney Test. * P < 0.05, ** P < 0.01, *** P < 0.001.