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β-Arrestin-2-Dependent Signaling Promotes CCR4-mediated Chemotaxis of Murine T-Helper Type 2 Cells.

Publication ,  Journal Article
Lin, R; Choi, YH; Zidar, DA; Walker, JKL
Published in: American journal of respiratory cell and molecular biology
June 2018

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 β-arrestin (β-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 β-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 β-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 β-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 β-arr2-dependent signaling and support β-arr2 as a novel therapeutic target in asthma.

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Published In

American journal of respiratory cell and molecular biology

DOI

EISSN

1535-4989

ISSN

1044-1549

Publication Date

June 2018

Volume

58

Issue

6

Start / End Page

745 / 755

Related Subject Headings

  • beta-Arrestin 2
  • Th2 Cells
  • Signal Transduction
  • Respiratory System
  • Receptors, CCR4
  • Pyridines
  • Mice, Knockout
  • Male
  • Enzyme Inhibitors
  • Chemotaxis
 

Citation

APA
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Lin, R., Choi, Y. H., Zidar, D. A., & Walker, J. K. L. (2018). β-Arrestin-2-Dependent Signaling Promotes CCR4-mediated Chemotaxis of Murine T-Helper Type 2 Cells. American Journal of Respiratory Cell and Molecular Biology, 58(6), 745–755. https://doi.org/10.1165/rcmb.2017-0240oc
Lin, Rui, Yeon Ho Choi, David A. Zidar, and Julia K. L. Walker. “β-Arrestin-2-Dependent Signaling Promotes CCR4-mediated Chemotaxis of Murine T-Helper Type 2 Cells.American Journal of Respiratory Cell and Molecular Biology 58, no. 6 (June 2018): 745–55. https://doi.org/10.1165/rcmb.2017-0240oc.
Lin R, Choi YH, Zidar DA, Walker JKL. β-Arrestin-2-Dependent Signaling Promotes CCR4-mediated Chemotaxis of Murine T-Helper Type 2 Cells. American journal of respiratory cell and molecular biology. 2018 Jun;58(6):745–55.
Lin, Rui, et al. “β-Arrestin-2-Dependent Signaling Promotes CCR4-mediated Chemotaxis of Murine T-Helper Type 2 Cells.American Journal of Respiratory Cell and Molecular Biology, vol. 58, no. 6, June 2018, pp. 745–55. Epmc, doi:10.1165/rcmb.2017-0240oc.
Lin R, Choi YH, Zidar DA, Walker JKL. β-Arrestin-2-Dependent Signaling Promotes CCR4-mediated Chemotaxis of Murine T-Helper Type 2 Cells. American journal of respiratory cell and molecular biology. 2018 Jun;58(6):745–755.

Published In

American journal of respiratory cell and molecular biology

DOI

EISSN

1535-4989

ISSN

1044-1549

Publication Date

June 2018

Volume

58

Issue

6

Start / End Page

745 / 755

Related Subject Headings

  • beta-Arrestin 2
  • Th2 Cells
  • Signal Transduction
  • Respiratory System
  • Receptors, CCR4
  • Pyridines
  • Mice, Knockout
  • Male
  • Enzyme Inhibitors
  • Chemotaxis