A CD22–Shp1 phosphatase axis controls integrin β7 display and B cell function in mucosal immunity
| Autor: | Ningguo Feng, Yuhan Bi, Eugene C. Butcher, Martin Brennan, Klaus Ley, Clare L. Abram, Lars Nitschke, Harry B. Greenberg, Borja Ocón, Alex Marki, Carolin Brandl, Clifford A. Lowell, Matthew S. Macauley, Romain Ballet, Takeshi Tsubata, Julian Cheng, Amin Alborzian Deh Sheikh, Jeremy Berri |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
biology Chemistry Lymphocyte Immunology CD22 Integrin Protein tyrosine phosphatase Endocytosis 3. Good health Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure hemic and lymphatic diseases medicine biology.protein Immunology and Allergy Lymphocyte homing receptor Intracellular B cell 030215 immunology |
| Zdroj: | Nature Immunology. 22:381-390 |
| ISSN: | 1529-2916 1529-2908 |
| Popis: | The integrin α4β7 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 α4β7 surface expression and gut immunity. Shp1 selectively inhibited β7 endocytosis, enhancing surface α4β7 display and lymphocyte homing to GALT. In B cells, CD22 associated in a sialic acid-dependent manner with integrin β7 on the cell surface to target intracellular Shp1 to β7. Shp1 restrained plasma membrane β7 phosphorylation and inhibited β7 endocytosis without affecting β1 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 α4β7 and in homing to GALT. Consistent with the specialized role of α4β7 in intestinal immunity, CD22 deficiency selectively inhibited intestinal antibody and pathogen responses. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink