Extended Data Fig. 2: The type I IFN response induced by Anxa1-deficient mice requires ATP-binding cassette transporter ABCG2.
(a) Scheme for KO-143 treatment of Anxa1CKO AP mice induced with 7 hourly injections of cerulein. (b) Pancreas histology scores of PBS- and KO-143-treated saline-control (Control) or AP mice. (c) Immunoblot analysis of ABCG2, c-Casp3, IFN-β, p-TBK1, TBK1, p-IRF3, IRF3, p-P65, and P65 in pancreas tissues of PBS- and KO-143-treated AP mice. (d) Anxa1CKO Abcg+/+ and Anxa1CKO Abcg2−/− mice were induced with 7 hourly injections of cerulein. (e) Immunoblot analysis of ABCG2, c-Casp3, IFN-β, p-TBK1, TBK1, p-IRF3, IRF3, p-P65, and P65 in pancreas tissues of cerulein-treated (AP) Anxa1CKO Abcg+/+ and Anxa1CKO Abcg2−/− mice. (f) Pancreas histology scores for Anxa1CKO Abcg+/+ and Anxa1CKO Abcg2−/−, saline-treated (NaCl) or AP mice. (g) Schematic sketch. Up: Anxa1 (A1) binds with high affinity to phosphatidylserine (PS) on the surface of apoptotic cells in a calcium (Ca+)-dependent manner, and contributes to the engulfment of apoptotic cells by efferocytosis of macrophages. Down: The deficiency of Anxa1 in macrophages impairs the clearance of apoptotic cells, triggering increased cGAMP production in the apoptotic or necrotic acinar cells which in turn enters the macrophages through ABCG2 transporter and activates STING/TBK1/NFκB signaling to induce the production of type I IFN. Data are presented as means ± SD of n = 5 (b, d) biologically independent samples per group. P values were determined by one-way ANOVA with Tukey’s post-hoc test (B.D). Illustrations in a and d created with Figdraw.com.
