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IFN-? and CD46 stimulation are associated with active lupus and skew natural T regulatory cell differentiation to type 1 regulatory T (Tr1) cells.


ABSTRACT: Immune suppressive activities exerted by regulatory T-cell subsets have several specific functions, including self-tolerance and regulation of adaptive immune reactions, and their dysfunction can lead to autoimmune diseases and contribute to AIDS and cancer. Two functionally distinct regulatory T-cell subsets are currently identified in peripheral tissues: thymus-developed natural T regulatory cells (nTregs) controlling self-tolerance and antiinflammatory IL-10-secreting type 1 regulatory T cells (Tr1) derived from Ag-stimulated T cells, which regulate inflammation-dependent adaptive immunity and minimize immunopathology. We establish herein that cell contact-mediated nTreg regulatory function is inhibited by inflammation, especially in the presence of the complement C3b receptor (CD46). Instead, as with other T-cell subsets, the latter inflammatory conditions of stimulation skew nTreg differentiation to Tr1 cells secreting IL-10, an effect potentiated by IFN-?. The clinical relevance of these findings was verified in a study of 152 lupus patients, in which we showed that lupus nTreg dysfunction is not due to intrinsic defects but is rather induced by C3b stimulation of CD46 and IFN-? and that these immune components of inflammation are directly associated with active lupus. These results provide a rationale for using anti-IFN-? Ab immunotherapy in lupus patients.

SUBMITTER: Le Buanec H 

PROVIDER: S-EPMC3223453 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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IFN-α and CD46 stimulation are associated with active lupus and skew natural T regulatory cell differentiation to type 1 regulatory T (Tr1) cells.

Le Buanec Hélène H   Gougeon Marie-Lise ML   Mathian Alexis A   Lebon Pierre P   Dupont Jean-Michel JM   Peltre Gabriel G   Hemon Patrice P   Schmid Michel M   Bizzini Bernard B   Künding Thomas T   Burny Arsène A   Bensussan Armand A   Amoura Zahir Z   Gallo Robert C RC   Zagury Daniel D  

Proceedings of the National Academy of Sciences of the United States of America 20111107 47


Immune suppressive activities exerted by regulatory T-cell subsets have several specific functions, including self-tolerance and regulation of adaptive immune reactions, and their dysfunction can lead to autoimmune diseases and contribute to AIDS and cancer. Two functionally distinct regulatory T-cell subsets are currently identified in peripheral tissues: thymus-developed natural T regulatory cells (nTregs) controlling self-tolerance and antiinflammatory IL-10-secreting type 1 regulatory T cell  ...[more]

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