Cargando…
A CD22-Shp1 phosphatase axis controls integrin β(7) display and B cell function in mucosal immunity
The integrin α(4)β(7) selectively regulates lymphocyte trafficking and adhesion in the gut and gut-associated lymphoid tissues (GALT). Here we describe unexpected involvement of tyrosine phosphatase Shp1 and the B cell lectin CD22 (Siglec 2) in regulation of α(4)β(7) surface expression and gut immun...
| Autores principales: | , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2021
|
| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116842/ https://www.ncbi.nlm.nih.gov/pubmed/33589816 http://dx.doi.org/10.1038/s41590-021-00862-z |
| _version_ | 1783514250237444096 |
|---|---|
| author | Ballet, Romain Brennan, Martin Brandl, Carolin Feng, Ningguo Berri, Jeremy Cheng, Julian Ocón, Borja Sheikh, Amin Alborzian Deh Marki, Alex Bi, Yuhan Abram, Clare L. Lowell, Clifford A. Tsubata, Takeshi Greenberg, Harry B. Macauley, Matthew S. Ley, Klaus Nitschke, Lars Butcher, Eugene C. |
| author_facet | Ballet, Romain Brennan, Martin Brandl, Carolin Feng, Ningguo Berri, Jeremy Cheng, Julian Ocón, Borja Sheikh, Amin Alborzian Deh Marki, Alex Bi, Yuhan Abram, Clare L. Lowell, Clifford A. Tsubata, Takeshi Greenberg, Harry B. Macauley, Matthew S. Ley, Klaus Nitschke, Lars Butcher, Eugene C. |
| author_sort | Ballet, Romain |
| collection | PubMed |
| description | The integrin α(4)β(7) selectively regulates lymphocyte trafficking and adhesion in the gut and gut-associated lymphoid tissues (GALT). Here we describe unexpected involvement of tyrosine phosphatase Shp1 and the B cell lectin CD22 (Siglec 2) in regulation of α(4)β(7) surface expression and gut immunity. Shp1 selectively inhibited β(7) endocytosis, enhancing surface α(4)β(7) display and lymphocyte homing to GALT. In B cells, CD22 associated in a sialic acid-dependent manner with integrin β(7) on the cell surface to target intracellular Shp1 to β(7). Shp1 restrained plasma membrane β(7) phosphorylation and inhibited β(7) endocytosis without affecting β(1) integrin. B cells with reduced Shp1 activity, B cells lacking CD22, or B cells expressing CD22 with mutated Shp1-binding or carbohydrate-binding domains displayed parallel reductions in surface α(4)β(7) and in homing to GALT. Consistent with the specialized role of α(4)β(7) in intestinal immunity, CD22 deficiency selectively inhibited intestinal antibody and pathogen responses. |
| format | Online Article Text |
| id | pubmed-7116842 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-71168422021-08-15 A CD22-Shp1 phosphatase axis controls integrin β(7) display and B cell function in mucosal immunity Ballet, Romain Brennan, Martin Brandl, Carolin Feng, Ningguo Berri, Jeremy Cheng, Julian Ocón, Borja Sheikh, Amin Alborzian Deh Marki, Alex Bi, Yuhan Abram, Clare L. Lowell, Clifford A. Tsubata, Takeshi Greenberg, Harry B. Macauley, Matthew S. Ley, Klaus Nitschke, Lars Butcher, Eugene C. Nat Immunol Article The integrin α(4)β(7) selectively regulates lymphocyte trafficking and adhesion in the gut and gut-associated lymphoid tissues (GALT). Here we describe unexpected involvement of tyrosine phosphatase Shp1 and the B cell lectin CD22 (Siglec 2) in regulation of α(4)β(7) surface expression and gut immunity. Shp1 selectively inhibited β(7) endocytosis, enhancing surface α(4)β(7) display and lymphocyte homing to GALT. In B cells, CD22 associated in a sialic acid-dependent manner with integrin β(7) on the cell surface to target intracellular Shp1 to β(7). Shp1 restrained plasma membrane β(7) phosphorylation and inhibited β(7) endocytosis without affecting β(1) integrin. B cells with reduced Shp1 activity, B cells lacking CD22, or B cells expressing CD22 with mutated Shp1-binding or carbohydrate-binding domains displayed parallel reductions in surface α(4)β(7) and in homing to GALT. Consistent with the specialized role of α(4)β(7) in intestinal immunity, CD22 deficiency selectively inhibited intestinal antibody and pathogen responses. 2021-03-01 2021-02-15 /pmc/articles/PMC7116842/ /pubmed/33589816 http://dx.doi.org/10.1038/s41590-021-00862-z Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| spellingShingle | Article Ballet, Romain Brennan, Martin Brandl, Carolin Feng, Ningguo Berri, Jeremy Cheng, Julian Ocón, Borja Sheikh, Amin Alborzian Deh Marki, Alex Bi, Yuhan Abram, Clare L. Lowell, Clifford A. Tsubata, Takeshi Greenberg, Harry B. Macauley, Matthew S. Ley, Klaus Nitschke, Lars Butcher, Eugene C. A CD22-Shp1 phosphatase axis controls integrin β(7) display and B cell function in mucosal immunity |
| title | A CD22-Shp1 phosphatase axis controls integrin β(7) display and B cell function in mucosal immunity |
| title_full | A CD22-Shp1 phosphatase axis controls integrin β(7) display and B cell function in mucosal immunity |
| title_fullStr | A CD22-Shp1 phosphatase axis controls integrin β(7) display and B cell function in mucosal immunity |
| title_full_unstemmed | A CD22-Shp1 phosphatase axis controls integrin β(7) display and B cell function in mucosal immunity |
| title_short | A CD22-Shp1 phosphatase axis controls integrin β(7) display and B cell function in mucosal immunity |
| title_sort | cd22-shp1 phosphatase axis controls integrin β(7) display and b cell function in mucosal immunity |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116842/ https://www.ncbi.nlm.nih.gov/pubmed/33589816 http://dx.doi.org/10.1038/s41590-021-00862-z |
| work_keys_str_mv | AT balletromain acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT brennanmartin acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT brandlcarolin acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT fengningguo acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT berrijeremy acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT chengjulian acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT oconborja acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT sheikhaminalborziandeh acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT markialex acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT biyuhan acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT abramclarel acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT lowellclifforda acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT tsubatatakeshi acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT greenbergharryb acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT macauleymatthews acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT leyklaus acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT nitschkelars acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT butchereugenec acd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT balletromain cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT brennanmartin cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT brandlcarolin cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT fengningguo cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT berrijeremy cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT chengjulian cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT oconborja cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT sheikhaminalborziandeh cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT markialex cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT biyuhan cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT abramclarel cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT lowellclifforda cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT tsubatatakeshi cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT greenbergharryb cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT macauleymatthews cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT leyklaus cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT nitschkelars cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity AT butchereugenec cd22shp1phosphataseaxiscontrolsintegrinb7displayandbcellfunctioninmucosalimmunity |