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March1-dependent modulation of donor MHC II on CD103+ dendritic cells mitigates alloimmunity

Author

Listed:
  • Thiago J. Borges

    (Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS. Av. Ipiranga
    Harvard Medical School
    Harvard Medical School)

  • Naoka Murakami

    (Harvard Medical School)

  • Felipe D. Machado

    (Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS. Av. Ipiranga)

  • Ayesha Murshid

    (Harvard Medical School)

  • Benjamin J. Lang

    (Harvard Medical School)

  • Rafael L. Lopes

    (Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS. Av. Ipiranga)

  • Laura M. Bellan

    (Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS. Av. Ipiranga)

  • Mayuko Uehara

    (Harvard Medical School)

  • Krist H. Antunes

    (Biomedical Research Institute, PUCRS. Av. Ipiranga)

  • Maria José Pérez-Saéz

    (Harvard Medical School)

  • Gabriel Birrane

    (Harvard Medical School)

  • Priscila Vianna

    (Universidade Federal do Rio Grande do Sul)

  • João Ismael B. Gonçalves

    (Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS. Av. Ipiranga
    La Salle University)

  • Rafael F. Zanin

    (Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS. Av. Ipiranga
    La Salle University)

  • Jamil Azzi

    (Harvard Medical School)

  • Reza Abdi

    (Harvard Medical School)

  • Satoshi Ishido

    (Hyogo College of Medicine)

  • Jeoung-Sook Shin

    (University of California San Francisco)

  • Ana Paula D. Souza

    (Harvard Medical School)

  • Stuart K. Calderwood

    (Harvard Medical School)

  • Leonardo V. Riella

    (Harvard Medical School)

  • Cristina Bonorino

    (Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS. Av. Ipiranga
    Federal University of Health Sciences of Porto Alegre)

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.

Suggested Citation

  • Thiago J. Borges & Naoka Murakami & Felipe D. Machado & Ayesha Murshid & Benjamin J. Lang & Rafael L. Lopes & Laura M. Bellan & Mayuko Uehara & Krist H. Antunes & Maria José Pérez-Saéz & Gabriel Birra, 2018. "March1-dependent modulation of donor MHC II on CD103+ dendritic cells mitigates alloimmunity," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05572-z
    DOI: 10.1038/s41467-018-05572-z
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    Cited by:

    1. Xuan Wang & Yingqi Liu & Chencheng Xue & Yan Hu & Yuanyuan Zhao & Kaiyong Cai & Menghuan Li & Zhong Luo, 2022. "A protein-based cGAS-STING nanoagonist enhances T cell-mediated anti-tumor immune responses," Nature Communications, Nature, vol. 13(1), pages 1-22, December.

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