Fig. 4: Enhanced SI LP Treg development and function upon Zfp36 deletion in dendritic cells. | Mucosal Immunology

Fig. 4: Enhanced SI LP Treg development and function upon Zfp36 deletion in dendritic cells.

From: The RNA-binding protein tristetraprolin regulates RALDH2 expression by intestinal dendritic cells and controls local Treg homeostasis

Fig. 4

a, b Flow cytometry results in WT or Zfp36-V5 epitope tagged knock-in mice, using an anti-V5 antibody. a Proportion of V5+ cells in different immune cell populations (n = 3–7 mice/group, pooled from three independent experiments) and epithelial cells (n = 10 mice/group, pooled from three independent experiments) in the small intestine (SI) at steady state. b Mean fluorescence intensity of V5 in conventional dendritic cells type 1 (cDC1: MHCII+CD11c+CD103+CD11b cells) and monocytes (CD11b+Ly6C+Ly6G) from lymphoid organs (spleen, mesenteric lymph nodes) or barrier organs (SI LP, lung) (n = 6-7 mice/group from two independent experiments). In MLN, cDCs were further differentiated into migratory (mig) or residential (res) subtypes. ch Flow cytometry results in conditional Zfp36 knock-out mice strains (CD11c-Cre Zfp36fl/fl: Zfp36ΔDC and LysM-Cre Zfp36fl/fl: Zfp36ΔM) and their control Zfp36flox/flox (fl/fl) mice. c Proportion of Tregs (Foxp3+ cells) among CD4 T cells in SI LP (n = 18–37 mice/group, pooled from 3–5 independent experiments). d Proportion of IL-10 producing Foxp3+ Tregs in SI LP (n = 7 mice/group, pooled from three independent experiments). e Increased peripheral Treg differentiation in SI LP from Zfp36ΔDC mice in an oral tolerance model: Zfp36fl/fl or Zfp36ΔDC mice were fed for 6 days with ovalbumin, after transfer of naive CD4+OTII+ cells sorted from OTII mice (n = 5–7 mice/group, pooled from two independent experiments). f Zfp36fl/fl and Zfp36ΔDC mice were infected with ten cysts of T. gondii and sacrificed 7 days later to proceed to flow cytometry and RTqPCR experiments (g, h) (n = 5–7 control mice or 16–18 infected mice, from three independent experiments). g Proportion of Tregs (Foxp3+ cells) among CD4 T cells in spleen, MLN, and SI LP. h Proportion of Tbet+ cells among Foxp3 CD4 T cells in spleen, MLN, and SI LP. Results are given as median ± interquartile range and each dot represents a single mouse. Statistical significance (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0,0001) was assessed by two-way ANOVA (a: WT vs. Zfp36-V5 tagged mice, b: MFI in SI LP from Zfp36-V5 tagged mice compared with MFI in other organs, g, h), by Kruskal–Wallis (c) or by Mann–Whitney test (d, e).

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