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

被引：20

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

共 70 条

[11] CTLA4-Ig Restores Rejection of MHC Class-II Mismatched Allografts by Disabling IL-2-Expanded Regulatory T Cells
Charbonnier, L. -M.
Vokaer, B.
Lemaitre, P. H.
Field, K. A.
Leo, O.
Le Moine, A.
[J]. AMERICAN JOURNAL OF TRANSPLANTATION, 2012, 12 (09) : 2313 - 2321
[12] A three-cell model for activation of naive T helper cells
Corthay, A.
[J]. SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 2006, 64 (02) : 93 - 96
[13] THE PRIMARY STRUCTURE OF MEK, A PROTEIN-KINASE THAT PHOSPHORYLATES THE ERK GENE-PRODUCT
CREWS, CM
ALESSANDRINI, A
ERIKSON, RL
[J]. SCIENCE, 1992, 258 (5081) : 478 - 480
[14] MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation
De Gassart, Aude
Camosseto, Voahirana
Thibodeau, Jacques
Ceppi, Maurizio
Catalan, Nadia
Pierre, Philippe
Gatti, Evelina
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (09) : 3491 - 3496
[15] Accelerated Antibody-Mediated Graft Loss of Rodent Pancreatic Islets After Pretreatment With Dexamethasone-Treated Immature Donor Dendritic Cells
de Kort, Hanneke
Crul, Cynthia
van der Wal, Annemieke M.
Schlagwein, Nicole
Stax, Annelein M.
Bruijn, Jan A.
van Kooten, Cees
de Heer, Emile
[J]. TRANSPLANTATION, 2012, 94 (09) : 903 - 910
[16] Mycobacterial heat shock protein 70 induces interleukin-10 production: immunomodulation of synovial cell cytokine profile and dendritic cell maturation
Detanico, T
Rodrigues, L
Sabritto, AC
Keisermann, M
Bauer, ME
Zwickey, H
Bonorino, C
[J]. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2004, 135 (02) : 336 - 342
[17] Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8α+ conventional dendritic cells
Edelson, Brian T.
Wumesh, K. C.
Juang, Richard
Kohyama, Masako
Benoit, Loralyn A.
Klekotka, Paul A.
Moon, Clara
Albring, Joern C.
Ise, Wataru
Michael, Drew G.
Bhattacharya, Deepta
Stappenbeck, Thaddeus S.
Holtzman, Michael J.
Sung, Sun-Sang J.
Murphy, Theresa L.
Hildner, Kai
Murphy, Kenneth M.
[J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2010, 207 (04) : 823 - 836
[18] Donor Intervention and Organ Preservation: Where Is the Science and What Are the Obstacles?
Feng, S.
[J]. AMERICAN JOURNAL OF TRANSPLANTATION, 2010, 10 (05) : 1155 - 1162
[19] Targeting co-stimulatory pathways: transplantation and autoimmunity
Ford, Mandy L.
Adams, Andrew B.
Pearson, Thomas C.
[J]. NATURE REVIEWS NEPHROLOGY, 2014, 10 (01) : 14 - 24
[20] Immunosuppressive drugs for kidney transplantation
Halloran, PF
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (26) : 2715 - 2729

← 1 2 3 4 5 6 7 →