Role of TGF-β in Self-Peptide Regulation of Autoimmunity.
Document Type
Article
Publication Date
2-2018
JAX Location
Reprint Collection
JAX Source
Arch Immunol Ther Exp (Warsz) 2018 Feb; 66(1):11-19
Volume
66
Issue
1
First Page
11
Last Page
19
ISSN
1661-4917
PMID
28733878
DOI
https://doi.org/10.1007/s00005-017-0482-6
Grant
DK27722
Abstract
Transforming growth factor (TGF)-β has been implicated in regulation of the immune system, including autoimmunity. We have found that TGF-β is readily produced by T cells following immunization with self-peptide epitopes that downregulate autoimmune responses in type 1 diabetes (T1D) prone nonobese diabetic (NOD) mice. These include multiple peptide epitopes derived from the islet β-cell antigens GAD65 (GAD65 p202-221, GAD65 p217-236), GAD67 (GAD67 p210-229, GAD67 p225-244), IGRP (IGRP p123-145, IGRP p195-214) and insulin B-chain (Ins. B:9-23) that protected NOD mice from T1D. Immunization of NOD mice with the self-MHC class II I-Ag7 β-chain-derived peptide, I-Aβg7 p54-76 also induced large amounts of TGF-β and also protected these mice from diabetes development. These results indicate that peptides derived from disease related self-antigens and MHC class II molecules primarily induce TGF-β producing regulatory Th3 and Tr1-like cells. TGF-β produced by these cells could enhance the differentiation of induced regulatory iTreg and iTreg17 cells to prevent induction and progression of autoimmune diseases. We therefore suggest that peripheral immune tolerance could be induced and maintained by immunization with self-peptides that induce TGF-β producing T cells. Arch Immunol Ther Exp (Warsz) 2018 Feb; 66(1):11-19.
Recommended Citation
Singh B,
Krawetz M,
De Lima R,
Mukherjee R,
Chaturvedi P,
Lee-Chan E,
Leiter EH,
Summers K.
Role of TGF-β in Self-Peptide Regulation of Autoimmunity. Arch Immunol Ther Exp (Warsz) 2018 Feb; 66(1):11-19