VIP and tolerance induction in autoimmunity.
Vasoactive intestinal peptide (VIP) is a potent anti-inflammatory agent with immunoregulatory properties, skewing the immune response to a Th2 pattern of cytokine production. Here, we studied the effect of treatment with VIP in the development of diabetes in nonobese diabetic (NOD) mice, an animal model of type 1 diabetes. Mice treated with VIP from 4 weeks of age did not develop diabetes and showed milder insulitis than nontreated mice. The protective mechanism of VIP was associated with a reduction in the circulating levels of Th1 cytokines. In the pancreas of VIP-treated animals, regulatory T cell markers predominate, as indicated by the upregulation of FoxP3 and transforming growth factor-beta (TGF-beta), and the downregulation of the transcription factor, T-bet. These findings indicate that VIP restores tolerance to pancreatic islets by promoting the local differentiation and function of regulatory T cells.
Rosignoli
F
F
Dept. Biología Celular, Facultad de Biologia, UCM 28040 Madrid, Spain.
Torroba
M
M
Juarranz
Y
Y
García-Gómez
M
M
Martinez
C
C
Gomariz
R P
RP
Pérez-Leirós
C
C
Leceta
J
J
D000818:Animals; D015551:Autoimmunity / Q000187:drug effects* / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D003920:Diabetes Mellitus / Q000378:metabolism / Q000517:prevention & control; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology*; D007328:Insulin / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007328:Insulin; D016212:Transforming Growth Factor beta; D014660:Vasoactive Intestinal Peptide