title: Protective Role of β-arrestin2 in Colitis Through Modulation of T-cell Activation.
abstract: β-arrestin2 (β-arr2), identified as a scaffolding protein in G-protein-coupled receptor desensitization, is a negative regulator of inflammation in polymicrobial sepsis. In this study, we wanted to investigate the role of β-arr2 in intestinal inflammation, a site of persistent microbial stimulation. In the absence of β-arr2, mice exhibited greater extent of mucosal inflammation determined by cellular infiltration and expression of inflammatory mediators even under homeostatic conditions. Furthermore, β-arr2-deficient mice were more susceptible to dextran sulfate sodium-induced colitis as demonstrated by greater body weight loss, higher disease activity index, and shortened colon as compared with wild-type mice. We also show that T cells from β-arr2 knockout mice exhibit altered activation status under both basal and colitic conditions, implicating their involvement in disease induction. Further assessment of the role of β-arr2 in intrinsic T-cell differentiation confirmed its importance in T-cell polarization. Using the T-cell transfer model of colitis, we demonstrate that T-cell-specific β-arr2 is important in limiting colitic inflammation; however, it plays a paradoxical role in concurrent systemic wasting disease. Together, our study highlights a critical negative regulatory role of β-arr2 in intestinal inflammation and demonstrates a distinct role of T-cell-specific β-arr2 in systemic wasting disease.
authors: *Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan †Department of Physiology and Division of Pathology, Michigan State University, East Lansing, Michigan; and ‡Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Deepika
authors: D
authors: Sharma
authors: Ankit
authors: A
authors: Malik
authors: Michael D
authors: MD
authors: Steury
authors: Peter C
authors: PC
authors: Lucas
authors: Narayanan
authors: N
authors: Parameswaran
mesh_terms: D000818:Animals; D019390:Arrestins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D016264:Dextran Sulfate; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D007422:Intestines / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000378:metabolism*; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
chemical_list: C000605258:Arrb2 protein, mouse; D019390:Arrestins; D018836:Inflammation Mediators; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D016264:Dextran Sulfate