In:
Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 27, No. 7 ( 2016-7), p. 1933-1942
Kurzfassung:
Chemokines and chemokine receptors are implicated in regulatory T cell (Treg) trafficking to sites of inflammation and suppression of excessive immune responses in inflammatory and autoimmune diseases; however, the specific requirements for Treg migration into the inflamed organs and the positioning of these cells within the tissue are incompletely understood. Here, we report that Tregs expressing the T H 1–associated chemokine receptor CXCR3 are enriched in the kidneys of patients with ANCA–associated crescentic GN and colocalize with CXCR3 + effector T cells. To investigate the functional role of CXCR3 + Tregs, we generated mice that lack CXCR3 in Tregs specifically (Foxp3 eGFP-Cre × Cxcr3 fl/fl ) and induced experimental crescentic GN. Treg-specific deletion of CXCR3 resulted in reduced Treg recruitment to the kidney and an overwhelming T H 1 immune response, with an aggravated course of the nephritis that was reversible on anti-IFN γ treatment. Together, these findings show that a subset of Tregs expresses CXCR3 and thereby, acquires trafficking properties of pathogenic CXCR3 + T H 1 cells, allowing Treg localization and control of excessive T H 1 responses at sites of inflammation.
Materialart:
Online-Ressource
ISSN:
1046-6673
,
1533-3450
DOI:
10.1681/ASN.2015020203
Sprache:
Englisch
Verlag:
Ovid Technologies (Wolters Kluwer Health)
Publikationsdatum:
2016
ZDB Id:
2029124-3