Tryptophan catabolism generates autoimmune-preventive regulatory T cells.
Tryptophan catabolism is a tolerogenic effector system in regulatory T cell function, yet the general mechanisms whereby tryptophan catabolism affects T cell responses remain unclear. We provide evidence that its effects include the emergence of a regulatory phenotype in naive CD4(+)CD25(-) cells via the general control non-depressing 2 (GCN2) protein kinase mediated induction of the forkhead transcription factor Foxp3. These cells are capable of effective control of diabetogenic T cells in vivo.
Fallarino
Francesca
F
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy. fllfnc@tin.it
Grohmann
Ursula
U
You
Sylvaine
S
McGrath
Barbara C
BC
Cavener
Douglas R
DR
Vacca
Carmine
C
Orabona
Ciriana
C
Bianchi
Roberta
R
Belladonna
Maria L
ML
Volpi
Claudia
C
Fioretti
Maria C
MC
Puccetti
Paolo
P
D000818:Animals; D015551:Autoimmunity; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D018448:Models, Immunological; D017346:Protein Serine-Threonine Kinases / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014364:Tryptophan / Q000276:immunology* / Q000378:metabolism*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014364:Tryptophan; C070634:Eif2ak4 protein, mouse; D017346:Protein Serine-Threonine Kinases