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

Channakeshava Sokke Umeshappa, Santiswarup Singha, Jesus Blanco, Kun Shao, Roopa Hebbandi Nanjundappa, Jun Yamanouchi, Albert Parés, Pau Serra, Yang Yang and Pere Santamaria ()
Additional contact information
Channakeshava Sokke Umeshappa: University of Calgary
Santiswarup Singha: University of Calgary
Jesus Blanco: Institut D’Investigacions Biomèdiques August Pi i Sunyer
Kun Shao: University of Calgary
Roopa Hebbandi Nanjundappa: University of Calgary
Jun Yamanouchi: University of Calgary
Albert Parés: Institut D’Investigacions Biomèdiques August Pi i Sunyer
Pau Serra: Institut D’Investigacions Biomèdiques August Pi i Sunyer
Yang Yang: University of Calgary
Pere Santamaria: University of Calgary

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-09893-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09893-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-09893-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().