Integrin-dependent regulation of gene expression in leukocytes

Grazisa Rossetti, Mark Collinge, Raffaela Molteni, Jeffrey R. Bender, Ruggero Pardi

Research output: Contribution to journalArticle

Abstract

In addition to their role in strengthening intercellular adhesion, leukocyte inntegrins transduce signals which affect genetic programs, consequendy defining cell phenotype and function. These signals can be independendy 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 αLβ2 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.

Original languageEnglish
Pages (from-to)189-207
Number of pages19
JournalImmunological Reviews
Volume186
DOIs
Publication statusPublished - Aug 2002

ASJC Scopus subject areas

  • Immunology

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