Programming of Distinct Chemokine-Dependent and -Independent Search Strategies for Th1 and Th2 Cells Optimizes Function at Inflamed Sites
| Autor: | Justin Schumacher, Angela Hughson, Ninoshka R. J. Fernandes, Hannah S. Bell, James H. Miller, Alan V. Smrcka, Christopher S. Anderson, Hen Prizant, Deborah J. Fowell, Brandon L. Walling, Alison Gaylo-Moynihan, Milan Popovic, Minsoo Kim, Kevin Chiou, David J. Topham, Tara Capece, Dillon C. Schrock |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Chemokine Cellular differentiation Immunology Cell Integrin Motility Lymphocyte Activation Article Mice 03 medical and health sciences Th2 Cells 0302 clinical medicine Cell Movement medicine Animals Humans Immunology and Allergy Cellular Reprogramming Techniques Receptor Cells Cultured G protein-coupled receptor Inflammation Mice Knockout Mice Inbred BALB C biology Effector Cell Differentiation Th1 Cells Integrin alphaVbeta3 Adoptive Transfer Cell biology Mice Inbred C57BL 030104 developmental biology Infectious Diseases medicine.anatomical_structure 030220 oncology & carcinogenesis biology.protein Chemokines STAT6 Transcription Factor |
| Zdroj: | Immunity |
| ISSN: | 1074-7613 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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