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

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

  • Immunity. 2019 Aug 20;51(2):298-309.e6. doi: 10.1016/j.immuni.2019.06.026.
Alison Gaylo-Moynihan 1,  Hen Prizant 1,  Milan Popović 1,  Ninoshka R J Fernandes 2,  Christopher S Anderson 1,  Kevin K Chiou 3,  Hannah Bell 1,  Dillon C Schrock 1,  Justin Schumacher 4,  Tara Capece 1,  Brandon L Walling 1,  David J Topham 1,  Jim Miller 1,  Alan V Smrcka 5,  Minsoo Kim 1,  Angela Hughson 1,  Deborah J Fowell 6
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 4 Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA.
  • 5 Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA.
  • 6 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: [email protected].
PMID: 31399281 DOI: 10.1016/j.immuni.2019.06.026
Abstract

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 αVβ3 expression: Th2 cell differentiation led to high αVβ3 expression relative to Th1 cells. Th1 and Th2 cell modes of motility could be switched simply by manipulating the amount of αVβ3 on the cell surface. Deviating motility modes from those established during differentiation impaired effector function. Thus, programmed expression of αVβ3 tunes effector T cell reliance on environmental cues for optimal exploration of inflamed tissues.

Keywords

GPCR; STAT6; Th differentiation; Th1; Th2; chemokine; inflammation; integrin; interstitial motility; skin.

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