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. 2022 Oct 7;8(40):eabn6552. doi: 10.1126/sciadv.abn6552

Fig. 4. ORAI1 controls the expression of cell cycle regulators and T cell proliferation during allergic airway inflammation.

Fig. 4.

(A) Numbers of up-regulated (↑) or down-regulated (↓) DEGs in OT-II T cells of WT and Orai1fl/flCd4Cre mice at days 9 and 14 after IAVOVA (x31) infection and HDM/OVA treatment, respectively (Fig. 3, A and B). (B and C) Analysis of WT and Orai1fl/flCd4Cre T cells at day 14 of HDM/OVA treatment (Fig. 3B). (B) Top six dysregulated pathways obtained by IPA, BioCarta, Gene Ontology, and KEGG, ranked by P values. Cell cycle–related pathways are shown in blue. ATM, ataxia telangiectasia mutated; NER, nucleotide excision repair; NES, normalized enrichment score; Plk3, Polo-like kinase 3. (C) GSEA of KEGG cell cycle (M7963) and hallmark G2-M checkpoint (M5901). (D) Normalized RNA-seq–based gene expression from the KEGG pathways cell cycle and DNA replication in T cells after IAVOVA infection and HDM/OVA treatment. (E to G) Analysis of WT and Orai1fl/flCd4Cre T cells at day 14 of HDM/OVA treatment. (E) IPA upstream regulator analysis of DEG ranked by P value. Colors indicate the activation Z score. Key regulators are highlighted in bold. (F) GSEA of E2F targets (M5925). (G) Epigenetic Landscape In Silico deletion Analysis (LISA) of transcriptional regulators of DEG ranked by P value. Key regulators are highlighted in bold. (H to J) Antigen-specific T cell proliferation after HDM treatment. (H) Experimental protocol. (I) Representative flow cytometry plot of CD4+CD44+ T cells after BrdU incorporation and staining with I-Ab tetramers (HDM-TCR+). (J) Frequencies of CD4+CD44+BrdU+HDM-TCR+ T cells from three WT and three Orai1fl/flCd4Cre mice. (K) Control of cell cycle progression by ORAI1. Inhibitors are highlighted in red, activators in blue. Statistical analysis in (B) and (E) is performed by Fisher’s exact test: P < 0.1; that in (D) is performed by ANOVA (Sidak’s multiple comparisons); that in (F) is performed by a Wilcoxon rank sum test; and that in (I) is performed by unpaired Student’s t test. **P < 0.01; *P < 0.05.