Kukan Emily N, Fabiano Gabrielle L, Glendenning Leandre M, Zhou Julie Y, Telfer Kevin A, Paulson James C, Cobb Brian A
School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
The Scripps Research Institute, San Diego, California, USA.
FASEB J. 2025 Jul 15;39(13):e70767. doi: 10.1096/fj.202500146RR.
The sialic acid/Siglec axis is an important immunologic regulatory pathway in which host-specific α2,6-sialylated glycans are recognized as markers of self. CD22, known primarily as a surface receptor on B cells, directly prevents autoantigen responses through concurrent recognition of α2,6-linked sialic acids. Here, we report that CD22 is expressed in macrophages polarized to an M2-like, immunomodulatory phenotype. Tissue-resident macrophage populations classically showing an M2-like skew, such as in the lung, were found to be significantly enriched for CD22 expression. We also discovered that CD22 promotes efferocytosis of sialylated glycoproteins and apoptotic debris and is associated with increased protein processing but reduced T cell activation. These findings support a model whereby CD22 M2-like macrophages participate in the resolution of inflammation and a return to tissue homeostasis via the clearance of host-derived α2,6-sialylated debris, degrading this material without further exacerbation of T cell-mediated inflammation.
唾液酸/唾液酸结合免疫球蛋白样凝集素（Siglec）轴是一条重要的免疫调节途径，其中宿主特异性α2,6-唾液酸化聚糖被识别为自身标记。CD22主要作为B细胞表面受体为人所知，它通过同时识别α2,6-连接的唾液酸直接阻止自身抗原反应。在此，我们报告CD22在极化为M2样免疫调节表型的巨噬细胞中表达。经典地表现出M2样偏向的组织驻留巨噬细胞群体，如在肺中，被发现CD22表达显著富集。我们还发现CD22促进唾液酸化糖蛋白和凋亡碎片的胞葬作用，并与蛋白质加工增加但T细胞活化减少有关。这些发现支持了一个模型，即CD22 M2样巨噬细胞通过清除宿主来源的α2,6-唾液酸化碎片参与炎症的消退和恢复组织稳态，降解这种物质而不会进一步加剧T细胞介导的炎症。
