A Context-Dependent Role for αv Integrins in Regulatory T Cell Accumulation at Sites of Inflammation.

Autor:	Mair I; MRC Centre for Inflammation Research, Centre for Multiple Sclerosis Research, BHF Centre for Cardiovascular Science, and Centre for Immunity Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom., Zandee SEJ; MRC Centre for Inflammation Research, Centre for Multiple Sclerosis Research, BHF Centre for Cardiovascular Science, and Centre for Immunity Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom., Toor IS; MRC Centre for Inflammation Research, Centre for Multiple Sclerosis Research, BHF Centre for Cardiovascular Science, and Centre for Immunity Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom., Saul L; MRC Centre for Inflammation Research, Centre for Multiple Sclerosis Research, BHF Centre for Cardiovascular Science, and Centre for Immunity Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom., McPherson RC; MRC Centre for Inflammation Research, Centre for Multiple Sclerosis Research, BHF Centre for Cardiovascular Science, and Centre for Immunity Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom., Leech MD; MRC Centre for Inflammation Research, Centre for Multiple Sclerosis Research, BHF Centre for Cardiovascular Science, and Centre for Immunity Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom., Smyth DJ; MRC Centre for Inflammation Research, Centre for Multiple Sclerosis Research, BHF Centre for Cardiovascular Science, and Centre for Immunity Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom., O'Connor RA; MRC Centre for Inflammation Research, Centre for Multiple Sclerosis Research, BHF Centre for Cardiovascular Science, and Centre for Immunity Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom., Henderson NC; MRC Centre for Inflammation Research, Centre for Multiple Sclerosis Research, BHF Centre for Cardiovascular Science, and Centre for Immunity Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom., Anderton SM; MRC Centre for Inflammation Research, Centre for Multiple Sclerosis Research, BHF Centre for Cardiovascular Science, and Centre for Immunity Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2018 Feb 26; Vol. 9, pp. 264. Date of Electronic Publication: 2018 Feb 26 (Print Publication: 2018).
DOI:	10.3389/fimmu.2018.00264
Abstrakt:	Several inflammatory diseases including multiple sclerosis and inflammatory bowel disease have been associated with dysfunctional and/or reduced numbers of Foxp3 + regulatory T cells (Treg). While numerous mechanisms of action have been discovered by which Treg can exert their function, disease-specific Treg requirements remain largely unknown. We found that the integrin αv, which can pair with several β subunits including β8, is highly upregulated in Treg at sites of inflammation. Using mice that lacked αv expression or β8 expression specifically in Treg, we demonstrate that there was no deficit in Treg accumulation in the central nervous system during experimental autoimmune encephalomyelitis and no difference in the resolution of disease compared to control mice. In contrast, during a curative T cell transfer model of colitis, Treg lacking all αv integrins were found at reduced proportions and numbers in the inflamed gut. This led to a quantitative impairment in the ability of αv-deficient Treg to reverse disease when Treg numbers in the inflamed colon were below a threshold. Increase of the number of curative Treg injected was able to rescue this phenotype, indicating that αv integrins were not required for the immunosuppressive function of Treg per se . In accordance with this, αv deficiency did not impact on the capacity of Treg to suppress proliferation of naive conventional T cells in vitro as well as in vivo . These observations demonstrate that despite the general upregulation of αv integrins in Treg at sites of inflammation, they are relevant for adequate Treg accumulation only in specific disease settings. The understanding of disease-specific mechanisms of action by Treg has clear implications for Treg-targeted therapies.
Databáze:	MEDLINE
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