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. Epub 2019 Aug 6.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cell Differentiation
  • Cell Movement
  • Cells, Cultured
  • Cellular Reprogramming Techniques
  • Chemokines / metabolism
  • Humans
  • Inflammation / immunology*
  • Integrin alphaVbeta3 / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • STAT6 Transcription Factor / metabolism
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*


  • Chemokines
  • Integrin alphaVbeta3
  • STAT6 Transcription Factor