| First Author | Lin R | Year | 2018 |
| Journal | Am J Respir Cell Mol Biol | Volume | 58 |
| Issue | 6 | Pages | 745-755 |
| PubMed ID | 29361236 | Mgi Jnum | J:275652 |
| Mgi Id | MGI:6313484 | Doi | 10.1165/rcmb.2017-0240OC |
| Citation | Lin R, et al. (2018) beta-Arrestin-2-Dependent Signaling Promotes CCR4-mediated Chemotaxis of Murine T-Helper Type 2 Cells. Am J Respir Cell Mol Biol 58(6):745-755 |
| abstractText | Allergic asthma is a complex inflammatory disease that leads to significant healthcare costs and reduction in quality of life. Although many cell types are implicated in the pathogenesis of asthma, CD4(+) T-helper cell type 2 (Th2) cells are centrally involved. We previously reported that the asthma phenotype is virtually absent in ovalbumin-sensitized and -challenged mice that lack global expression of beta-arrestin (beta-arr)-2 and that CD4(+) T cells from these mice displayed significantly reduced CCL22-mediated chemotaxis. Because CCL22-mediated activation of CCR4 plays a role in Th2 cell regulation in asthmatic inflammation, we hypothesized that CCR4-mediated migration of CD4(+) Th2 cells to the lung in asthma may use beta-arr-dependent signaling. To test this hypothesis, we assessed the effect of various signaling inhibitors on CCL22-induced chemotaxis using in vitro-polarized primary CD4(+) Th2 cells from beta-arr2-knockout and wild-type mice. Our results show, for the first time, that CCL22-induced, CCR4-mediated Th2 cell chemotaxis is dependent, in part, on a beta-arr2-dependent signaling pathway. In addition, we show that this chemotactic signaling mechanism involves activation of P-p38 and Rho-associated protein kinase. These findings point to a proinflammatory role for beta-arr2-dependent signaling and support beta-arr2 as a novel therapeutic target in asthma. |
