alexa CTLA-4-Ig regulates tryptophan catabolism in vivo.


Journal of Clinical & Cellular Immunology

Author(s): Grohmann U, Orabona C, Fallarino F, Vacca C, Calcinaro F,

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Abstract Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a critical role in peripheral tolerance. However, regulatory pathways initiated by the interactions of CTLA-4 with B7 counterligands expressed on antigen-presenting cells are not completely understood. We show here that long-term survival of pancreatic islet allografts induced by the soluble fusion protein CTLA-4-immunoglobulin (CTLA-4-Ig) is contingent upon effective tryptophan catabolism in the host. In vitro, we show that CTLA-4-Ig regulates cytokine-dependent tryptophan catabolism in B7-expressing dendritic cells. These data suggest that modulation of tryptophan catabolism is a means by which CTLA-4 functions in vivo and that CTLA-4 acts as a ligand for B7 receptor molecules that transduce intracellular signals. This article was published in Nat Immunol and referenced in Journal of Clinical & Cellular Immunology

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