Programming of Distinct Chemokine-Dependent and -Independent Search Strategies for Th1 and Th2 Cells Optimizes Function at Inflamed Sites.

Autor: Gaylo-Moynihan A; David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA., Prizant H; David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA., Popović M; David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA., Fernandes NRJ; David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA; Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA., Anderson CS; David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA., Chiou KK; Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, PA 19104, USA., Bell H; David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA., Schrock DC; David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA., Schumacher J; Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA., Capece T; David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA., Walling BL; David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA., Topham DJ; David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA., Miller J; David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA., Smrcka AV; Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA., Kim M; David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA., Hughson A; David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA., Fowell DJ; David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA. Electronic address: deborah_fowell@urmc.rochester.edu.
Jazyk: angličtina
Zdroj: Immunity [Immunity] 2019 Aug 20; Vol. 51 (2), pp. 298-309.e6. Date of Electronic Publication: 2019 Aug 06.
DOI: 10.1016/j.immuni.2019.06.026
Abstrakt: T-helper (Th) cell differentiation drives specialized gene programs that dictate effector T cell function at sites of infection. Here, we have shown Th cell differentiation also imposes discrete motility gene programs that shape Th1 and Th2 cell navigation of the inflamed dermis. Th1 cells scanned a smaller tissue area in a G protein-coupled receptor (GPCR) and chemokine-dependent fashion, while Th2 cells scanned a larger tissue area independent of GPCR signals. Differential chemokine reliance for interstitial migration was linked to STAT6 transcription-factor-dependent programming of integrin α V β 3 expression: Th2 cell differentiation led to high α V β 3 expression relative to Th1 cells. Th1 and Th2 cell modes of motility could be switched simply by manipulating the amount of α V β 3 on the cell surface. Deviating motility modes from those established during differentiation impaired effector function. Thus, programmed expression of α V β 3 tunes effector T cell reliance on environmental cues for optimal exploration of inflamed tissues.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: