Lymphocytes are migratory cells
An intricate system to guide lymphocytes to areas of inflammation is involved.1 The imprinting of activated lymphocytes allows for preferential migration into tissues.1 This is achieved through the expression of integrins and chemokine receptors on lymphocytes and their respective ligands, adhesion molecules, and chemokines on vascular endothelium.2,3
Lymphocyte trafficking to the gut colitis
Several molecules are involved in the lymphocyte trafficking/adhesion cascade.3 However, only a few are responsible for gut specificity. Among these are α4β7 integrin and its ligand MAdCAM-1, and CCR9 chemokine receptor and its ligand CCL25.1,4
Lymphocyte trafficking requires a multistep adhesion cascade to gain access to tissues
Prior to entering tissues from the circulation, lymphocytes must engage several sequential adhesion pathways.3
- Initial tethering of lymphocytes is mediated via interactions between selectins, integrins, and their respective receptors3
Rolling and activation
- Rolling lymphocytes respond to chemoattractants, such as chemokines, through specific chemokine receptors3
- The signal induced by chemokine-chemokine receptor interactions can activate β2 and/or α4 integrins, which can subsequently bind to members of the endothelial immunoglobulin superfamily (eg, ICAM-1, ICAM-2, VCAM-1, and MAdCAM-1) and lead to the eventual arrest of the lymphocyte3
Salmi M, Jalkanen S. Lymphocyte homing to the gut: attraction, adhesion, and commitment. Immunol Rev. 2005;206:100-113.
Sheriden BS, Lefrançois L. Regional and mucosal memory T cells. Nat Immunol. 2011;12(6):485-491.
von Andrian UH, Mackay CR . T-cell function and migration. Two sides of the same coin.N Engl J Med. 2000;343(14):1020-1034.
Koenecke C, Förster R. CCR9 and inflammatory bowel disease. Expert Opin Ther Targets. 2009;13(3):297-306.
Janeway CA Jr, Travers P, Walport M, Shlomchik MJ. Immunobiology: The Immune System in Health and Disease. 6th ed. New York, NY: Garland Science Publishing; 2005.
Stedman’s Medical Dictionary. 27th ed. New York, NY: Lippincott Williams & Wilkins; 2000.
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Integrin: heterodimeric cell-surface protein involved in cell-cell and cell-matrix interactions; important in adhesive interactions between lymphocytes and antigen-presenting cells and in lymphocyte and leukocyte migration into tissues5
Chemokine: small chemoattractant protein that stimulates the migration and activation of cells, especially phagocytic cells and lymphocytes5
Lymphocytes: a class of white blood cells that bear variable cell-surface receptors for antigen; there are 2 main classes—B cells and T cells—which mediate humoral and cell-mediated immunity, respectively5
Ligand: a molecule that binds to a macromolecule (eg, binding to a receptor)6
Adhesion molecule: mediates the binding of one cell to other cells or to extracellular matrix proteins5
Selectin: a cell surface molecule involved in immune adhesion and cell trafficking6
Chemoattractant: chemical substance that influences the migration of cells6
Immunoglobulins: a family of plasma proteins to which antibody molecules belong5