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Title: Suppression of a broad spectrum of liver autoimmune pathologies by single peptide-MHC-based nanomedicines
Author: Sokke Umeshappa, Channakeshava
Singha, Santiswarup
López Blanco, José Manuel
Shao, Kun
Hebbandi Nanjundappa1, Roopa
Yamanouchi, Jun
Parés Darnaculleta, Albert
Serra, Pau
Yang, Yang
Santamaria, Pere
Keywords: Pèptids
Malalties autoimmunitàries
Cèl·lules T
Autoimmune diseases
T cells
Issue Date: 14-May-2019
Publisher: Nature Publishing Group
Abstract: Peptide-major histocompatibility complex class II (pMHCII)-based nanomedicines displaying tissue-specific autoantigenic epitopes can blunt specific autoimmune conditions by re-programming 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.
Note: Reproducció del document publicat a:
It is part of: Nature Communications, 2019, vol. 10, p. 2150
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ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Medicina)

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