Regulation of immune function by CD22 on antigen-presenting cells  

Sialic acid immunoglobin-like lectins (Siglecs) are a family of transmembrane proteins that can deliver activating or inhibitory signals necessary for an effective immune response. Interactions between sialic acids produced by ST6GAL1 and Siglec-2 (CD22) result in immune inactivation via immunoreceptor tyrosine-based inhibitory motifs (ITIMs). CD22 has been well-characterized as a regulator of B cell function. However, we now demonstrate that conventional type-2 dendritic cells (cDC2s) and hybrid macrophages in the spleen and tumor microenvironment (TME) express CD22. To understand the function of CD22 on APCs, we have generated novel CD22 floxed mice and crossed them to Zbtb46-Cre, which deletes CD22 on cDC2s and hybrid macrophages as well as CX₃CR1-Cre mice that delete CD22 in hybrid macrophages. Signals from APCs drive effective adaptive immune responses, including effective anti-tumor immune responses. For example, inhibited APCs are associated with poor prognosis and immunotherapeutic resistance to cancer. We propose that CD22 inhibits APC function, and modulating this interaction may improve immune responses. It has been previously shown that several cancers upregulate ST6GAL1. Using APC-specific CD22 cKO mice, we will utilize the subcutaneous flank tumor models and colitis-associated colorectal cancer (CAC) models to determine the function of CD22 in APCs in anti-tumor responses.