title: Integrin-dependent regulation of gene expression in leukocytes.
abstract: In addition to their role in strengthening intercellular adhesion, leukocyte integrins transduce signals which affect genetic programs, consequently defining cell phenotype and function. These signals can be independently sufficient, or can cooperate with other environmental stimuli to affect gene expression regulation. In the past several years, there has been an emergence of mechanistic data which contribute to our understanding of these critical integrin roles. In this review, we describe anchorage-dependent T lymphocyte proliferation and, in particular, how leukocyte integrin engagement overcomes the G1 to S cell cycle restriction point in antigen-activated T cells. The related role of alphaLbeta2 integrin (LFA-1) as a T cell co-stimulatory molecule is discussed. This includes defining mechanisms whereby LFA-1 engagement enhances transcriptional activation of numerous genes by regulating its association with transcription modulators such as JAB-1, and through interaction with other gene-activating signaling complexes such as JAK-STATs. Evidence is presented to support that leukocyte integrin engagement provides potent signals which stabilize otherwise labile activation mRNA transcripts, including those encoding cytokine and extracellular matrix degrading proteins. These integrin-dependent mechanisms, all described recently, play important roles in T cell differentiation and proliferation, immune surveillance and inflammatory responses.
authors.affiliation: Unit of Leukocyte Biology, Department of Molecular Biology and Functional Genomics, Vita-Salute San Raffaele University School of Medicine, Milan, Italy.
authors.forename: Grazisa
authors.initials: G
authors.lastname: Rossetti
authors.forename: Mark
authors.initials: M
authors.lastname: Collinge
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Bender
authors.forename: Raffaela
authors.initials: R
authors.lastname: Molteni
authors.forename: Ruggero
authors.initials: R
authors.lastname: Pardi
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D016023:Integrins / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D016023:Integrins