Integrins and their functions on hematopoietic cells. (A) The human integrin family consists of 24 heterodimers, composed of 18 α-subunits and 8 β-subunits; underscored are those subunits of which the heterodimer has not been detected on hematopoietic cells (α6β4, αvβ6, α7-11β1). The matching colors represent exemplary heterodimers together with a prototypic ligand and the biological process in which this receptor/ligand pair is involved (eg, the prototypic ligand of α4β1 is VCAM-1, which is involved in leukocyte extravasation). Integrins support diverse events in the hematopoietic life cycle, including maintenance of progenitors in the bone marrow niche, B- and T-cell proliferation, maturation and differentiation in the thymus and spleen, and homing/retention of tissue-resident leukocytes in the epithelia of the gut and skin. In addition, integrins are required for hemostasis, transforming growth factor-β activation, migration in and out of blood vessels or secondary lymphoid tissues, and migration through environments rich in collagens, laminins, and fibronectin. (B) Integrins also promote leukocyte effector functions by potentiating the formation of immunological synapses and cytokine production, as well as phagocytosis of apoptotic cells and (complement-opsonized) pathogens. (C) Integrins adopt 3 main conformations on the cell surface, with different affinities (low, intermediate, or high) for ligand. MadCAM, mucosal addressin cell adhesion molecule; MHC, major histocompatibility complex; SMAC, supramolecular activation cluster; TGF, transforming growth factor; VCAM, vascular cell adhesion molecule.