Suppression of a broad spectrum of liver autoimmune pathologies by single peptide-MHC-based nanomedicines.

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Umeshappa CS,Singha S,Blanco J,Shao K,Nanjundappa RH,Yamanouchi J,Parés A,Serra P,Yang Y,Santamaria P

doi

10.1038/s41467-019-09893-5

subject

Has Abstract

pub_date

2019-05-14 00:00:00

pages

2150

issue

1

issn

2041-1723

pii

10.1038/s41467-019-09893-5

journal_volume

10

pub_type

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