Fig. 7: Local and proximal LiNKTR1-driven Breg cell formation via cognate interactions. | Nature Communications

Fig. 7: Local and proximal LiNKTR1-driven Breg cell formation via cognate interactions.

From: Re-programming mouse liver-resident invariant natural killer T cells for suppressing hepatic and diabetogenic autoimmunity

Fig. 7

a, b Conversion of adoptively transferred eGFP– B cells from NOD.Il10-eGFP donors into eGFP+CD5+CD1dhi Bregs in the liver, PCLNs and MLNs of αGalCer/CD1d-NP- (n = 5) vs. Cys-NP-treated (n = 3) NOD.c3c4 mice in the absence (a) or presence (b) of isotype (n = 4) or anti-CD1d mAb (n = 5). In a, Left panels show representative flow cytometric plots for liver B cells, and right panels show average percentages of eGFP+CD5+ and eGFP+CD1dhi B cells within donor B cells. c Secretion of IL-10 and IL-35 by liver, PCLN and MLN B cells from Cys-NP- (n = 4) and αGalCer/CD1d-NP-treated (n = 5) NOD.c3c4 mice, in response to an LPS challenge ex vivo. d Secretion of IL-10 by liver, splenic and lung B cells from Cys-NP- (n = 5) and αGalCer/CD1d-NP-treated (n = 4) NOD.c3c4 mice, in response to an LPS challenge ex vivo. e, f Macroscopic (e) and microscopic (f) PBC scores in NOD.c3c4.scid hosts reconstituted with pooled splenocytes and PCLN cells from diseased NOD.c3c4 donors upon transfusion with pooled liver and PCLN B cells from Cys-NP- (n = 4) or αGalCer/CD1d-NP-treated donors (n = 6). g Average microscopic liver scores in NOD or NOD.B2mloxP.B2m–/– mice with hFTCD-induced AIH in response to treatment with Cys-NPs (n = 9, from 3 experiments) or αGalCer/CD1d-NPs (NOD mice: n = 15, from 4 experiments; NOD.B2mloxP.B2m–/– mice: n = 3). h Average microscopic AIH scores in NOD.B2mloxP.B2m–/– (n = 3), vs. NOD.B2mloxP.B2m–/–/CD19-cre mice (n = 4) in response to αGalCer/CD1d-NP treatment. i Secretion of IL-10 and IL-35 by PCLN- and MLN-derived B cells of the mice from g in response to an LPS challenge (n = 4, 4, and 3, respectively). j Secretion of IL-10 and IL-35 by PCLN- and MLN-derived B cells of the mice from h in response to an LPS challenge (n = 3 and 4, respectively). Data correspond to mean ± SEM. P values were calculated using one tail Mann–Whitney U (a–f, h, j) or one-way ANOVA with Tukey’s post hoc correction (g, i). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

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