Trafficking of leukocytes and their local activity profile are of pivotal importance for many (patho)physiological processes. Fittingly, microenvironments are complex by nature, with multiple mediators originating from diverse cell types and playing roles in an intimately regulated manner. To dissect aspects of this complexity, effectors are initially identified and structurally characterized, thus prompting familial classification and establishing foci of research activity. In this regard, chemokines present themselves as role models to illustrate the diversification and fine-tuning of inflammatory processes. This in turn discloses the interplay among chemokines, their cell receptors and cognate glycosaminoglycans, as well as their capacity to engage in new molecular interactions that form hetero-oligomers between themselves and other classes of effector molecules. The growing realization of versatility of adhesion/growth-regulatory galectins that bind to glycans and proteins and their presence at sites of inflammation led to testing the hypothesis that chemokines and galectins can interact with each other by protein–protein interactions. In this review, we present some background on chemokines and galectins, as well as experimental validation of this chemokine–galectin heterodimer concept exemplified with CXCL12 and galectin-3 as proof-of-principle, as well as sketch out some emerging perspectives in this arena.
Bibliographical noteFunding Information:
KHM is Van de Laar professor of structural biology?at Maastricht University, The Netherlands. KHM is also grateful to the Ludwig-Maximillian-University (LMU),?Munich, Germany, Center for Advanced Study and the Alexander von Humboldt Foundation, Berlin, Germany, for support during his 2019 sabbatical stay at the LMU.
Open Access funding enabled and organized by Projekt DEAL. This work was supported by the National Science Foundation (BIR-961477), the University of Minnesota Medical School and the Minnesota Medical Foundation (K.H.M) and by the Deutsche Forschungsgemeinschaft, SFB1123, A2 (HJG, PvH).
© 2021, The Author(s).