Ablation of CD22 induces a pro-inflammatory transcriptome shift and endocytic deficits in M2-like macrophages

Abstract The interactions between environmental glycans and glycan-binding proteins modulate a host of processes across biological systems. The Siglec/sialic acid axis has gained increasing attention as an immunologic checkpoint due to its involvement with reducing inflammatory processes and promoting tumor growth. Siglec-2, or CD22, has been extensively characterized as a co-receptor for the B cell receptor (BCR) and is critical for the prevention of self-reactive B cell responses through its recognition of α2,6-linked sialic acids. More recently, CD22 has emerged as an important receptor for macrophage biology. Here, we investigate the consequences of genetic ablation of CD22 in murine macrophages (CD22KO). Aged CD22KO mice developed a fatty liver phenotype similar to that seen in aged animals lacking hepatocyte α2,6-sialylation (HcKO). CD22KO bone marrow-derived macrophages (BMDMs) exhibited few differences in canonical markers of M1-like and M2-like polarization, but M2-like CD22KO BMDMs showed a pro-inflammatory shift in transcriptome and a reduction in endocytic and efferocytotic capacity. These data suggest that CD22 in murine M2-like macrophages is strongly associated with a homeostatic transcriptional profile and directly participates in immunologically silent housekeeping functions such as clearance of sialylated-self debris through the Siglec-sialic acid axis.