Siglec-F is a novel intestinal M cell marker

Abstract

Intestinal microfold (M) cells are epithelial cells primarily present on Peyer's patches (PPs) in the small intestine. The ability of M cells to shuttle antigens into the PP for appropriate immune responses makes M cells a target for next-generation oral vaccine delivery. In this regard, discovery of M cell-specific receptors are of great interest, which could act as molecular tags for targeted delivery of cargo to M cells. Here, using a monoclonal antibody we generated to the Sialic acid-binding immunoglobulin-like lectin F (Siglec-F), we show that Siglec-F is expressed on mouse M cells in the small intestine. Immunohistochemical analysis of the PP tissue sections shows that Siglec-F is expressed on the surface of the M cell membrane exposed to the intestinal lumen. Anti-Siglec-F antibody injected into the mouse small intestine bound to M cells, demonstrating the potential to target M cells via Siglec-F.

Frontline Science: Characterization of a novel mouse strain expressing human Siglec-8 only on eosinophils

“…In addition to eosinophils, alveolar macrophages and subtypes of gut epithelial cells also express Siglec-F in the mouse. [17][18][19] However, Siglec-F + gut epithelial cells, as expected, do not express Siglec-8 ( Fig. 2).…”

“…In the blood, bone marrow, spleen, peritoneal cavity, and gut lamina propria, Siglec-8 expression was observed on all eosinophils examined and only on eosinophils. That is, no Siglec-8 was detected on any other cell type, including other cell types that express Siglec-F, such as alveolar macrophages or specific subtypes of gut epithelial cells [17][18][19]. Both in vitro and in vivo, Siglec-8 is expressed relatively early in eosinophil development (d7 of culture or at the eosinophil progenitor (EoP) stage) in this mouse strain, which is consistent with its induction by EPX promoter activity.…”

“…However, antibody ligation of Siglec‐F can rapidly clear circulating eosinophils and reduces eosinophilic inflammation, and loss of endogenous sialoside ligands for Siglec‐F exacerbates eosinophilic inflammation . This study used a distinct anti‐Siglec‐F mAb clone (9C7, rat IgG2b) from studies that have examined the pro‐apoptotic effect of Siglec‐F and, in order to compare Siglec‐F targeting more directly with Siglec‐8 targeting, used a slightly lower, yet saturating concentration of anti‐Siglec‐F than other studies. It is possible that, due to increased efficacy, the provision of small amounts of Siglec‐8 targeting agents will allow Siglec‐8 to more than adequately compensate for the loss of Siglec‐F.…”

“…12,30,31 However, antibody ligation of Siglec-F can rapidly clear circulating eosinophils and reduces eosinophilic inflammation, 30,32,33 and loss of endogenous sialoside ligands for Siglec-F exacerbates eosinophilic inflammation. 34,35 This study used a distinct anti-Siglec-F mAb clone (9C7, rat IgG2b) 18…”

Glycobiology of Eosinophilic Inflammation: Contributions of Siglecs, Glycans, and Other Glycan-Binding Proteins

“…Using monoclonal antibodies to Siglec-F, it was found that Siglec-F, like Siglec-8, was predominantly expressed on the surface of mature eosinophils and on bone marrow eosinophils ( 54 ). However, Siglec-F is not expressed on mouse mast cells and surprisingly is instead expressed on mouse alveolar macrophages and subpopulations of intestinal epithelial cells ( 55 – 57 ) (Figure 3 ). Although they are structurally different and are expressed on different cell types, Siglec-F, like Siglec-8, has a binding preference for α2-3-linked sialic acids and recognizes 6′-sulfo-sLe x ( 58 ).…”