Integrins in immunity

Abstract

A successful immune response depends on the capacity of immune cells to travel from one location in the body to another–these cells are rapid migrators, travelling at speeds of μm/minute. Their ability to penetrate into tissues and to make contacts with other cells depends chiefly on the β2 integrin known as LFA-1. For this reason, we describe the control of its activity in some detail. For the non-immunologist, the fine details of an immune response often seem difficult to fathom. However, the behaviour of immune cells, known as leukocytes (Box 1), is subject to the same biological rules as many other cell types, and this holds true particularly for the functioning of the integrins on these cells. In this Commentary, we highlight, from a cell-biology point of view, the integrin-mediated immune-cell migration and cell-cell interactions that occur during the course of an immune response.

Integrin CD11b Negatively Regulates TLR9-Triggered Dendritic Cell Cross-Priming by Upregulating microRNA-146a

“…Integrins are special molecules that have outside-in and inside-out pathways mediated by their conformational changes (bent: inactive; extended: intermediate affinity; extended with open conformation: high affinity) (13,14). CD11b is widely expressed in DCs, NK cells, macrophages, and activated CTLs.…”

“…According to their distinct a subunits, they are divided into four functional heterodimers termed LFA-1 (CD11a/CD18, aLb2 integrin, ITAL Ag), Mac-1 (CD11b/CD18, aMb2 integrin, ITAM Ag), p150,95 (CD11c/CD18, aXb2 integrin, CR4, ITAX Ag), and aDb2 (CD11d/CD18, ITAD Ag). CD11b is extensively expressed in most immune cells, such as DCs, monocytes/macrophages, granulocytes, and NK cells, and it participates in cell activation, chemotaxis, cytotoxicity, and phagocytosis (13,14). Our previous reports showed that CD11b is able to maintain immunological tolerance and inhibit inflammatory responses by repressing TLR3 signaling in NK cells and TLR4 signaling in macrophages (15,16).…”

Integrins as therapeutic targets: lessons and opportunities

“…1), bind to a diverse collection of ligands which are mostly large molecules, usually found in the subendothelial matrix, including fibronectin 1 , vitronectin 9 and collagen 10 . Other ligands are plasma proteins including complement factors 11 , C-reactive protein 12 and fibrinogen 13 . Many integrins also recognize the amino acid sequence Arg-Gly-Asp (RGD) in their ligands 2,14 .…”

“…Integrins have a key role in the migration and interaction of cells of the immune system. Both β 1 and β 2 integrins are important in immune function where they play essential roles in localizing the immune response to the site of inflammation 11 and a defect in β 2 integrins leads to life-threatening immune dysfunction (leucocyte adhesion deficiency, LAD) 32 . Engagement of the T-cell receptor and subsequent inside-out signalling leads to activation of T-cell integrins 18 .…”

“…Recent evidence suggests that inhibition of both α V β 3 and α 5 β 1 may be required for optimum effects on angiogenesis 71 . 11 . However, the role of integrins in infection has yet to be exploited for therapeutic purposes but inhibition of these interactions, which are involved in the infection process, has a potential role in the treatment of infection.…”