A CD22-Shp1 Phosphatase Axis Controls Integrin β Display and B Cell Function in Mucosal Immunity

Overview

Journal Nat Immunol

Date 2021 Feb 16

PMID 33589816

Citations 9

Authors

Romain Ballet

Martin Brennan

Carolin Brandl

Ningguo Feng

Jeremy Berri

Julian Cheng

Borja Ocon

Amin Alborzian Deh Sheikh

Alex Marki

Yuhan Bi

Clare L Abram

Clifford A Lowell

Takeshi Tsubata

Harry B Greenberg

Matthew S Macauley

Klaus Ley

Lars Nitschke

Eugene C Butcher

Affiliations

Soon will be listed here.

Abstract

The integrin αβ 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 αβ surface expression and gut immunity. Shp1 selectively inhibited β endocytosis, enhancing surface αβ display and lymphocyte homing to GALT. In B cells, CD22 associated in a sialic acid-dependent manner with integrin β on the cell surface to target intracellular Shp1 to β. Shp1 restrained plasma membrane β phosphorylation and inhibited β endocytosis without affecting β 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 αβ and in homing to GALT. Consistent with the specialized role of αβ in intestinal immunity, CD22 deficiency selectively inhibited intestinal antibody and pathogen responses.

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