期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-09893-5
关键词
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资金
- Crohn's and Colitis Foundation of Canada (CCFC)
- Canadian Institutes of Health Research (CIHR)
- FEDER [PIE14/00027, PI15/0797]
- Ministerio de Economia y Competitividad of Spain [MINECO SAF2015-68187-R]
- Generalitat de Catalunya (SGR Program)
- Generalitat de Catalunya (CERCA Program)
- CIHR
- Alberta Innovates-Health Solutions (AI-HS)
- Banting-CIHR fellowships
- Banting-CIHR
- AI-HS
- Rio Hortega (MINECO) fellowship
- European Foundation for the Study of Diabetes (EFSD-Lilly) fellowship
- JDRF Career Development Award
- Diabetes Association (Foothills)
- Diabetes Canada
- ISCIII
Peptide-major histocompatibility complex class II (pMHCII)-based nanomedicines displaying tissue-specific autoantigenic epitopes can blunt specific autoimmune conditions by reprogramming cognate antigen-experienced CD4+ T-cells into disease-suppressing T-regulatory type 1 (TR1) cells. Here, we show that single pMHCII-based nanomedicines displaying epitopes from mitochondrial, endoplasmic reticulum or cytoplasmic antigens associated with primary biliary cholangitis (PBC) or autoimmune hepatitis (AIH) can broadly blunt PBC, AIH and Primary Sclerosing Cholangitis in various murine models in an organ- rather than disease-specific manner, without suppressing general or local immunity against infection or metastatic tumors. Therapeutic activity is associated with cognate TR1 cell formation and expansion, TR1 cell recruitment to the liver and draining lymph nodes, local B-regulatory cell formation and profound suppression of the pro-inflammatory capacity of liver and liver-proximal myeloid dendritic cells and Kupffer cells. Thus, autoreactivity against liver-enriched autoantigens in liver autoimmunity is not disease-specific and can be harnessed to treat various liver autoimmune diseases broadly.
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