787 Endosomal GLUT3 is essential for macrophage signaling, polarization, and function in wound healing and atopic dermatitis

Macrophages are immune cells that play critical roles in both inflammation and tissue homeostasis. Classically activated (M1) macrophages promote antimicrobial tumoricidal activity, while alternatively (M2) phagocytosis The facilitative GLUT1 GLUT3 hexose transporters expressed abundantly different hematopoietic lineages, but their specific macrophages, leukocytes general is poorly understood. We discovered expression was increased after M2-activation stimuli macrophages. Notably, KO BMDM (bone marrow-derived macrophages) showed marked defects M2, not M1, polarization. Consistent with M2 polarization, impaired wound healing decreased calcipotriol-induced, atopic dermatitis-like inflammation. Mechanistically, we found the IL-4-STAT6 axis, main signaling pathway for strongly by deficiency. Unlike GLUT1, which localized to plasma membrane, GLUT3, along components of IL-4 pathway, endosomes. depletion a variety cancer cell lines revealed an essential role STAT3 signaling, suggesting broader regulation Thus, our studies reveal macrophage polarization function suggest more broadly conserved endosomal signaling.