Gut human REG3A promotes the formation of gut mucus layers. a Fluorescence in situ hybridization of 16S rRNA and immunostaining of mucin in the ileum of human REG3Atg mice (REG3A) and control cohoused littermate wt mice (ten slides/mouse; n = 6). b qRT-PCR of mucin 2 (MUC2) in the ileum of human REG3Atg and control cohoused littermate wt mice (n = 6). c Staining of goblet cells in the ileum of control cohoused littermate wt and human REG3Atg mice. Ten slides/mouse, n = 6; VCU, villus-crypt units. d QRT-PCR of Clca3, REtnlb, and Tff2 (n = 6). e Staining of Ki67 cells (ten slides/mouse, n = 6) and qRT-PCR of Cdknla and Cdkn2d (n = 6). f Crypt and transit-amplifying (TA) heights in the ileum of wt and human REG3Atg mice. Eighty wt (WT) versus 86 human REG3A tg (REG3A) transit-amplifying compartments; ten slides/mouse, n = 6. g Fluorescence in situ hybridization of 16S rRNA and immunostaining of mucin in the proximal colon of human REG3Atg mice (REG3A) and control cohoused littermate wt mice (ten slides/mouse; n = 6). h QRT-PCR of mucin 2 (MUC2) in the colon tissues (n = 6). i Staining of Ki67 cells in the colon (ten slides/mouse, n = 6) and qRT-PCR of Cdknla and Cdkn2d (n = 6). j, k Survival rate (j), body weight, and the disease activity index (DAI) (k) after DSS (n = 18). l Length of colon tissue. m QRT-PCR of TNFα, IL1®, and IL-6 in the colon tissues after DSS (n = 6). n Hematoxylin/eosin staining and histological scores of distal colon samples after DSS. Scale bars = 40 µm. o LPS in the peripheral sera of REG3Atg and control cohoused littermate wt mice after DSS (n = 6). p Bacterium clones in the spleen after DSS (n = 6). Student’s t test, mean ± SD in b, d, and e (RE), h, i (RE), and l, m, o, and p, mean ± SEM in e (ki67 cell), f, g, and i the Mann–Whitney U test in c and n; Wilcoxon’s test in j; analysis of variance test in k; NS no significance; RE relative expression. Data are representative of three independent experiments. Also see Supplementary Figs. 1 and 2