Fig. 8: Tfr cells dampen transplant rejection by limiting B cell production of IL-15. | Nature Communications

Fig. 8: Tfr cells dampen transplant rejection by limiting B cell production of IL-15.

From: Follicular regulatory T cells restrain kidney allograft rejection in mice by suppressing alloreactive B cells

Fig. 8

a Diagram of bulk RNAseq experiment. CD19+GL7+FAS+ GC B cells from dLN were sorted from CTLA4Ig and DT treated Tfr-Con or Tfr-DTR recipients and RNAseq performed. b Volcano plot indicating differentially expressed genes (DEGs) between Tfr-Con and Tfr-DTR GC B cells as in (a). Genes with a P value < 0.05 are shown highlighted as upregulated (red) or downregulated (blue) in Tfr-DTR. c KEGG pathways associated with DEGs from (b). d Concentration of IL-15 from interstitial fluid of dLNs from Tfr-Con (n = 5) and Tfr-DTR (n = 4) mice, expressed as a relative value to protein concentration. e Schematic of in vitro Tfh-mediated B cell stimulation assay. Tfh, Tfr, and B cells from transplant recipients were cocultured for 4 days with anti-CD3/IgM in the presence or absence of 100 ng/ml anti-IL-15. f Quantification of IL-15 levels in the supernatant from the co-culture assay described in (e). g Percentage of GL7+ B cells in the presence of Tfh cells under indicated co-culture conditions. h Quantification of IgG in the culture supernatants from culture conditions. i Schematic of experiment to assess the role of IL-15Rα in B cell alloimmunity after kidney transplantation. IL-15Rα KO (Il15ra-/-) or control mice received Balb/c kidney transplants, and grafts were harvested on day 20 for analysis, n = 4 per group. j Gating strategy (left) and quantification (right) of GL7+ GC B cells in the dLNs as in (i). n = 4 per group. k Schematic of experiment to assess contribution of IL-15 to exacerbated rejection after Tfr-deletion. Tfr-DTR mice underwent Balb/c kidney transplantation and received CTLA4Ig and DT. Some mice further received anti-IL-15. Mice were either followed for survival or organs harvested on day 20 post-transplantation for analysis. l Kaplan-Meier survival curve of transplanted Tfr-DTR recipients with or without anti-IL-15 treatment as in (k). m Total IgG DSA from the serum of mice as in (k) 20 days after transplantation. n = 4 per group. n Model summarizing Tfr role in controlling kidney transplant rejection. Red arrow indicates effect of Tfr cells. (a-c, i, j) Data is combined from two experiments. (d-h, k-m) Data is from two experiments and is representative of two independent experiments. Statistics: Error bars show mean ± SEM. Student’s two-tailed unpaired T test (d, j, m), One-way ANOVA with Tukey’s multiple comparison test for f-h. Kaplan-Meier survival analysis, and a log-rank test for survival analysis (l). Source data are provided as a Source Data file. Portions created in BioRender. Zhang, H. (2025) https://BioRender.com/b29q775.

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