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. 2024 May 13;15:1278197. doi: 10.3389/fimmu.2024.1278197

Figure 4.

Figure 4

PAD-induced immune dysregulation is associated with aberrant antigen presentation by ISCs and IECs. (A) A representative tSNE map of identifiable ISC and IEC subsets is shown. Four lineages (IEC, Paneth cells, FC ISCs, and FR ISCs) were subsequently gated based on their expression of MHCII and CD1d antigen presenting molecules. Heatmaps of MHCII and CD1d expression are provided to orient the reader to major shifts in the abundance of antigen-presenting IECs and ISCs shown in 4B. (B) Density tSNE plots highlighting differences in absolute IEC/ISC subset abundances are shown (each plot is generated from concatenated events from six mice). T and B cell deficient RAG1-/- and CD4-deficient MHCII-/- mice are provided as gating controls. (C) An MDS plot illustrating immunophenotypic variation among mouse strains based on IEC and ISC antigen-presenting phenotypes (left), and the relative contribution of differences in the absolute abundances of double-negative (CD1d-MHCII-)(DN), double-positive (CD1d+MHCII+)(DP), and single-positive (CD1d+MHCII- or CD1d-MHCII+)(SP) cell subsets in driving immune dysregulation (right) are shown. Kruskal-Wallis test, **=p<0.01, ****=p<0.0001. (D) The results of response screening analysis of immune phenotypes that significantly correlate (denoted by red bars) with the degree of immune dysregulation are shown. Significance reflects results of FDR-corrected p-values from multiple linear regression analysis of all 16 IEC/ISC subsets analyzed.