Fig. 7: Depletion of LZTR1 in KCs restricts NF-κB1 p50 binding to HLA class I promoter.
From: LZTR1 regulates epithelial MHC-I expression via NF-κB1 to modulate CD8+ T cells activation
a, b Hallmark pathway of TNFA_NFKB (a) and KRAS (b) signaling AUC score cluster distributions. c, d Violin plots of the AUC score in TNFA_NFKB (c) and KRAS (d) signaling in KCs. e–g IB analysis of the indicated proteins of NF-κB and MAPK signaling pathway in HaCaT after treatment with LZTR1 sgRNA (e), primary mouse KC (f), and mouse epidermis (g). h–n MFI level of membrane HLA-ABC or mRNA level of HLA-A, HLA-B in Ctrl and LZTR1 KO HaCaT treated with 5 μM NF-κB inhibitor QNZ (h–j), siNFKB1 (k, l) or overexpressed (oe)-NFKB1 (m, n). veh, vehicle (n = 2–4). o qPCR of H2-D1 and H2-K1 mRNA expression in KCs from mice treated with siNfkb1 and IFNγ (n = 4). p, q Schematic diagram of promoter site construction and results for dual luciferase assay of HLA-A (p) and HLA-B (q) with siNFKB1 or oe-NFKB1 (n = 3). r Relative enrichment fold of HLA-A and HLA-B promoter sequence immunoprecipitated with NF-κB1 in HaCaT analyzed by qPCR (n = 3). s NF-κB1 predictive binding site on HLA-A and HLA-B promoter. t Schematic diagram of NF-κB1-binding deficiency promoter construction. u–x Quantification of luciferase activity level of HLA-A and HLA-B in WT or mutant promoter combined with siNFKB1 (u, v) and LZTR1 KO (w, x) (n = 3). y Schematic mechanism diagram of LZTR1 regulating MHC-I. ns: not significant; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 by Wilcoxon rank test (c), one-way ANOVA (k) and two-way ANOVA (i, j, l, n–r, u–x). Data are shown as mean ± SEM.
