Fig. 6: LZTR1 modulates the function of CD8+ T cells by regulating the expression of MHC-I in KCs.
From: LZTR1 regulates epithelial MHC-I expression via NF-κB1 to modulate CD8+ T cells activation
a Dot plot of KEGG pathway enrichment on protein with downregulated phospho-site (FC <–1.3, P < 0.05) in Lztr1-deficient mice. Log2 Fold enrichment on the x axis indicates pathway enrichment value among downregulated proteins. b Feature plot of gene expression on total cells from mouse skin tissue. c MHC-I antigen presentation score on KCs. d–h Analysis of MHC-I molecular expression in HaCaT transfected with sgLZTR1 or CTRL sgRNA or primary KCs extracted from Lztr1-deficient or Control mice. IB (d) and FCM analysis (e, g) of MHC-I molecular membrane expression and quantification (f, h) (n = 3). i, j qPCR of mRNA encoding MHC-I molecular genes among HaCaT cell (i) (n = 5–6) and mice skin lesions (j) (n = 4). k IB analysis of MHC-I molecules in mouse epidermis tissue. l, m FCM of MHC-II molecular membrane expression in HaCaT (l) or primary mouse KCs (m). n, o qPCR analysis of MHC-II molecular genes among HaCaT (n) (n = 5) and mouse skin lesions (o) (n = 4). p, q IF images (p) and quantification (q) of CD8a number per sight (×200) and MHC-I expression (×100) in skin lesional sections. Scale bars, 100 μm (n = 3–4). r Linear regression analysis of LZTR1 and HLA-A, HLA-B, HLA-C mRNA expression among psoriasis lesion and healthy control based on GSE13355. s Box plot showing mRNA expression levels of IL17A, CD4, and CD8A in samples from patients with psoriasis divided into “LZTR1low” group (low half of expression) and “LZTR1high” group (top half of expression) based on GSE13355. t Experimental schedule. Each mouse was intracutaneously injected with AAV2-Ctrl or AAV2-H2-D1 on each ear and then treated with 15 mg cream containing 5% IMQ onto each ear daily for another 6 days. u Ear thickness change (n = 5–6). v qPCR of mRNA encoding S100a9, Il17a in mouse skin lesions (n = 3). w, x H&E of ear lesion skin (w) and summary (x). Scale bars, 100 μm (n = 5–6). ns: not significant; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 by Wilcoxon rank test (c), two-tailed unpaired t-test (f, h–j, n, o, q, s), one-way ANOVA (v, x) and two-way ANOVA (u). Data are shown as mean ± SEM.
