Absence of BCAP in myeloid cells abrogates M2 macrophage differentiation and promotes anti-tumor immunity.

ABSTRACT: B-cell adaptor for PI3K (BCAP) is a critical signaling adapter that links Toll-like receptors (TLRs) to the phosphatidylinositol 3-kinase (PI3K)-Akt pathway and negatively regulates TLR-induced inflammation. BCAP also facilitates transition of macrophages from an inflammatory (M1) to a reparatory (M2) state; however, whether BCAP functions downstream of receptors that directly drive M2 macrophage differentiation is not known. Here, we find that BCAP is essential for M2 differentiation in response to interleukin (IL)-4 and IL-33. BCAP-deficient macrophages displayed an impaired M2 gene program, marked by reduced expression of Arg1, Retnla, and Mgl2. Mechanistically, BCAP enables IL-4-driven PI3K-Akt activation by mediating interactions between p85 and Grb2 without impac

SUBMITTER: Kawarizadeh K 

PROVIDER: S-EPMC12595122 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature