| First Author | Gaffal E | Year | 2014 |
| Journal | J Invest Dermatol | Volume | 134 |
| Issue | 8 | Pages | 2131-2137 |
| PubMed ID | 24577407 | Mgi Jnum | J:212136 |
| Mgi Id | MGI:5578111 | Doi | 10.1038/jid.2014.117 |
| Citation | Gaffal E, et al. (2014) beta-Arrestin 2 Inhibits Proinflammatory Chemokine Production and Attenuates Contact Allergic Inflammation in the Skin. J Invest Dermatol 134(8):2131-7 |
| abstractText | beta-Arrestins participate in G-protein receptor signaling and act as adapter proteins that direct the recruitment, activation, and scaffolding of various cytoplasmic signaling complexes. beta-Arrestin 2-deficient (Arrb2(-/-)) mice show decreased T-cell recruitment into allergic lung tissue but increased neutrophil infiltration into wounded skin. Given these opposing effects in different immune cell subsets, we investigated the role of beta-arrestin 2 in the regulation of contact hypersensitivity responses. We observed significantly increased allergic ear swelling to the obligate contact sensitizers DNFB and FITC in Arrb2(-/-) compared with wild-type mice. Immunohistological analyses revealed strikingly increased neutrophil infiltration with abundant subcorneal pustules in inflamed ear tissue of DNFB-allergic Arrb2(-/-) mice. Experiments involving adoptive transfers of sensitized lymphocytes and bone marrow chimeric mice indicated that beta-arrestin 2 exerts its anti-inflammatory effects predominantly through radioresistant, skin-resident cells in the challenge phase of contact hypersensitivity. As a potential mechanism, we found that primary cultures of beta-arrestin 2-deficient keratinocytes secreted higher levels of neutrophil-attracting chemokines including CXCL1/KC in response to T cell-derived cytokines in vitro. These experimental results support a model in which beta-arrestin 2 inhibits the production of proinflammatory chemokines, which limits the recruitment of myeloid immune cells and thereby attenuates allergic skin inflammation. |
