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.
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Authors | Deepika Sharma, Ankit Malik, Michael D Steury, Peter C Lucas, Narayanan Parameswaran |
Journal | Inflammatory bowel diseases
(Inflamm Bowel Dis)
Vol. 21
Issue 12
Pg. 2766-77
(Dec 2015)
ISSN: 1536-4844 [Electronic] England |
PMID | 26296063
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Arrb2 protein, mouse
- Arrestins
- Inflammation Mediators
- beta-Arrestin 2
- beta-Arrestins
- Dextran Sulfate
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Topics |
- Animals
- Arrestins
(deficiency, genetics, immunology)
- Colitis
(chemically induced, genetics, immunology)
- Dextran Sulfate
- Inflammation Mediators
(metabolism)
- Intestinal Mucosa
(immunology, pathology)
- Intestines
(immunology, pathology)
- Lymphocyte Activation
- Mice
- Mice, Knockout
- T-Lymphocytes
(metabolism)
- beta-Arrestin 2
- beta-Arrestins
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