| First Author | Ballet R | Year | 2021 |
| Journal | Nat Immunol | Volume | 22 |
| Issue | 3 | Pages | 381-390 |
| PubMed ID | 33589816 | Mgi Jnum | J:305265 |
| Mgi Id | MGI:6705809 | Doi | 10.1038/s41590-021-00862-z |
| Citation | Ballet R, et al. (2021) A CD22-Shp1 phosphatase axis controls integrin beta7 display and B cell function in mucosal immunity. Nat Immunol 22(3):381-390 |
| abstractText | The integrin alpha4beta7 selectively regulates lymphocyte trafficking and adhesion in the gut and gut-associated lymphoid tissue (GALT). Here, we describe unexpected involvement of the tyrosine phosphatase Shp1 and the B cell lectin CD22 (Siglec-2) in the regulation of alpha4beta7 surface expression and gut immunity. Shp1 selectively inhibited beta7 endocytosis, enhancing surface alpha4beta7 display and lymphocyte homing to GALT. In B cells, CD22 associated in a sialic acid-dependent manner with integrin beta7 on the cell surface to target intracellular Shp1 to beta7. Shp1 restrained plasma membrane beta7 phosphorylation and inhibited beta7 endocytosis without affecting beta1 integrin. B cells with reduced Shp1 activity, lacking CD22 or expressing CD22 with mutated Shp1-binding or carbohydrate-binding domains displayed parallel reductions in surface alpha4beta7 and in homing to GALT. Consistent with the specialized role of alpha4beta7 in intestinal immunity, CD22 deficiency selectively inhibited intestinal antibody and pathogen responses. |
