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

被引：22

作者：

Borges, Thiago J. ^{[1
,2
,3
,4
]}

Murakami, Naoka ^{[3
]}

Machado, Felipe D. ^{[1
,2
]}

Murshid, Ayesha ^{[4
]}

Lang, Benjamin J. ^{[4
]}

Lopes, Rafael L. ^{[1
,2
]}

Bellan, Laura M. ^{[1
,2
]}

Uehara, Mayuko ^{[3
]}

Antunes, Krist H. ^{[5
,6
]}

Perez-Saez, Maria Jose ^{[3
]}

Birrane, Gabriel ^{[7
]}

Vianna, Priscila ^{[8
]}

Goncalves, Joao Ismael B. ^{[1
,2
,11
]}

Zanin, Rafael F. ^{[1
,2
,11
]}

Azzi, Jamil ^{[3
]}

Abdi, Reza ^{[3
]}

Ishido, Satoshi ^{[9
]}

Shin, Jeoung-Sook ^{[10
]}

Souza, Ana Paula D. ^{[7
]}

Calderwood, Stuart K. ^{[4
]}

Riella, Leonardo V. ^{[3
]}

Bonorino, Cristina ^{[1
,2
,12
]}

机构：

[1] Pontificia Univ Catolica Rio Grande do Sul, PUCRS, Sch Biosci, Lab 6, Ave Ipiranga,6690,IPB,2nd Floor, Porto Alegre, RS, Brazil

[2] Pontificia Univ Catolica Rio Grande do Sul, PUCRS, Biomed Res Inst, Lab 6, Ave Ipiranga,6690,IPB,2nd Floor, Porto Alegre, RS, Brazil

[3] Harvard Med Sch, Brigham & Womens Hosp, Renal Div, Schuster Family Transplantat Res Ctr, 221 Longwood Ave, Boston, MA 02115 USA

[4] Harvard Med Sch, Dept Radiat Oncol, Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA

[5] Pontificia Univ Catolica Rio Grande do Sul, Biomed Res Inst, Sch Pharm, Lab 31, Ave Ipiranga,6690,IPB,2nd Floor, Porto Alegre, RS, Brazil

[6] Pontificia Univ Catolica Rio Grande do Sul, Biomed Res Inst, Ctr Infant, Lab 31, Ave Ipiranga,6690,IPB,2nd Floor, Porto Alegre, RS, Brazil

[7] Harvard Med Sch, Dept Med, Beth Israel Deaconess Med Ctr, 99 Brookline Ave, Boston, MA 02215 USA

[8] Univ Fed Rio Grande do Sul, Genet Dept, Ave Bento Goncalves, BR-9500 Porto Alegre, RS, Brazil

[9] Hyogo Coll Med, Dept Microbiol, Nishinomiya, Hyogo 6638501, Japan

[10] Univ Calif San Francisco, Sandler Asthma Basic Res Ctr, Dept Microbiol & Immunol, 513 Parnassus Ave,HSE 201, San Francisco, CA 94143 USA

[11] La Salle Univ, Dept Hlth & Human Dev, Ave Victor Barreto, BR-2288 Canoas, RS, Brazil

[12] Fed Univ Hlth Sci Porto Alegre, Dept Basic Hlth Sci, Lab Immunotherapy, Rua Sarmento Leite, BR-245 Porto Alegre, RS, Brazil

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

TRANSCRIPTION FACTOR STAT3; ANTIGEN-PRESENTING CELLS; CD4; T-CELLS; IN-VIVO; TRANSPLANT TOLERANCE; INTERLEUKIN-10; PRODUCTION; ALLOGRAFT-REJECTION; LANGERHANS CELLS; DOWN-REGULATION; MACROPHAGES;

D O I：

10.1038/s41467-018-05572-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：15

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