March1-dependent modulation of donor MHC II on CD103+ dendritic cells mitigates alloimmunity
Abstract
In transplantation, donor dendritic cells (do-DCs) initiate the alloimmune response either by direct interaction with host T cells or by transferring intact donor MHC to host DCs. However, how do-DCs can be targeted for improving allograft survival is still unclear. Here we show CD103+ DCs are the major do-DC subset involved in the acute rejection of murine skin transplants. In the absence of CD103+ do-DCs, less donor MHC-II is carried to host lymph nodes, fewer allogenic T cells are primed and allograft survival is prolonged. Incubation of skin grafts with the anti-inflammatory mycobacterial protein DnaK reduces donor MHC-II on CD103+DCs and prolongs graft survival. This effect is mediated through IL-10-induced March1, which ubiquitinates and decreases MHC-II levels. Importantly, in vitro pre-treatment of human DCs with DnaK reduces their ability to prime alloreactive T cells. Our findings demonstrate a novel therapeutic approach to dampen alloimmunity by targeting donor MHC-II on CD103+DCs.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 28, 2018
- Source ID
- 10.1038/s41467-018-05572-z
Entities
People
- Ana Paula D. Souza
- Ayesha Murshid
- Benjamin J Lang
- Cristina Bonorino
- Felipe D. Machado
- Gabriel Birrane
- Jamil Azzi
- Jeoung-sook Shin
- João Ismael B. Gonçalves
- Krist H. Antunes
- Laura M Bellan
- Leonardo V Riella
- Maria José Pérez-saéz
- Mayuko Uehara
- Naoka Murakami
- Priscila Vianna
- Rafael F. Zanin
- Rafael L. Lopes
- Reza Abdi
- Satoshi Ishido
- Stuart K Calderwood
- Thiago J. Borges
Organizations
- American Heart Association
- Financiadora de Estudos e Projetos
- Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul
- United States Department of Defense