| First Author | Borges TJ | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 3482 |
| PubMed ID | 30154416 | Mgi Jnum | J:266483 |
| Mgi Id | MGI:6209258 | Doi | 10.1038/s41467-018-05572-z |
| Citation | Borges TJ, et al. (2018) March1-dependent modulation of donor MHC II on CD103(+) dendritic cells mitigates alloimmunity. Nat Commun 9(1):3482 |
| abstractText | 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. |
