Immune cell recruitment and migration is central to the normal functioning of the immune system in health and disease. Numerous adhesion molecules on immune cells and the parenchymal cells they interact with are well recognized for their roles in facilitating the movements of immune cells throughout the body. A growing body of evidence now indicates that tetraspanins, proteins known for their capacity to organize partner molecules within the cell membrane, also have significant impacts on the ability of immune cells to migrate around the body. In this review, we examine the tetraspanins expressed by immune cells and endothelial cells that influence leukocyte recruitment and motility and describe their impacts on the function of adhesion molecules and other partner molecules that modulate the movements of leukocytes. In particular, we examine the functional roles of CD9, CD37, CD63, CD81, CD82, and CD151. This reveals the diversity of the functions of the tetraspanin family in this setting, both in the nature of adhesive and migratory interactions that they regulate, and the positive or inhibitory effects mediated by the individual tetraspanin proteins.

Deciphering the molecular basis of leukocyte recruitment is critical to the understanding of inflammation. In this study, we investigated the contribution of the tetraspanin CD37 to this key process. CD37-deficient mice showed impaired neutrophil recruitment in a peritonitis model. Intravital microscopic analysis indicated that the absence of CD37 impaired the capacity of leukocytes to follow a CXCL1 chemotactic gradient accurately in the interstitium. Moreover, analysis of CXCL1-induced leukocyte-endothelial cell interactions in postcapillary venules revealed that CXCL1-induced neutrophil adhesion and transmigration were reduced in the absence of CD37, consistent with a reduced capacity to undergo β2 integrin–dependent adhesion. This result was supported by in vitro flow chamber experiments that demonstrated an impairment in adhesion of CD37-deficient neutrophils to the β2 integrin ligand, ICAM-1, despite the normal display of high-affinity β2 integrins. Superresolution microscopic assessment of localization of CD37 and CD18 in ICAM-1–adherent neutrophils demonstrated that these molecules do not significantly cocluster in the cell membrane, arguing against the possibility that CD37 regulates β2 integrin function via a direct molecular interaction. Moreover, CD37 ablation did not affect β2 integrin clustering. In contrast, the absence of CD37 in neutrophils impaired actin polymerization, cell spreading and polarization, dysregulated Rac-1 activation, and accelerated β2 integrin internalization. Together, these data indicate that CD37 promotes neutrophil adhesion and recruitment via the promotion of cytoskeletal function downstream of integrin-mediated adhesion.

CD53 is essential for lymph node cellularity as Cd53 À/À lymph nodes lack T and B cells CD53 is essential for lymphocyte homing to lymph nodes CD53 stabilizes L-selectin cell surface expression and may restrain shedding Impaired lymphocyte homing leads to diminished immune responses in Cd53 À/À mice