ADAP restraint of STAT1 signaling regulates macrophage phagocytosis in immune thrombocytopenia.

ABSTRACT: Heightened platelet phagocytosis by macrophages accompanied by an increase in IFN-γ play key roles in the etiology of immune thrombocytopenia (ITP); however, it remains elusive how macrophage-mediated platelet clearance is regulated in ITP. Here, we report that adhesion and degranulation-protein adaptor protein (ADAP) restrains platelet phagocytosis by macrophages in ITP via modulation of signal transducer and activator of transcription 1 (STAT1)-FcγR signaling. We show that ITP was associated with the underexpression of ADAP in splenic macrophages. Furthermore, macrophages from Adap^-/- mice exhibited elevated platelet phagocytosis and upregulated proinflammatory signaling, and thrombocytopenia in Adap^-/- mice was mitigated by the depletion of macrophages. Mechanistic

SUBMITTER: Xiong Y 

PROVIDER: S-EPMC9149338 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature