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CD11c+ Dendritic Cells Accelerate the Rejection of Older Cardiac Transplants via Interleukin-17A

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CD11c+ Dendritic Cells Accelerate the Rejection of Older Cardiac Transplants via Interleukin-17A. / Heinbokel, Timm; Oberhuber, Rupert; Cetina Biefer, Hector Rodriguez; Boenisch, Olaf; Hock, Karin; Bronson, Roderick T; Wilhelm, Markus J; Iwakura, Yoichiro; Edtinger, Karoline; Uehara, Hirofumi; Quante, Markus; Voskuil, Floris; Krenzien, Felix; Slegtenhorst, Bendix; Abdi, Reza; Pratschke, Johann; Elkhal, Abdallah; Tullius, Stefan G.

In: CIRCULATION, Vol. 132, No. 2, 14.07.2015, p. 122-31.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Heinbokel, T, Oberhuber, R, Cetina Biefer, HR, Boenisch, O, Hock, K, Bronson, RT, Wilhelm, MJ, Iwakura, Y, Edtinger, K, Uehara, H, Quante, M, Voskuil, F, Krenzien, F, Slegtenhorst, B, Abdi, R, Pratschke, J, Elkhal, A & Tullius, SG 2015, 'CD11c+ Dendritic Cells Accelerate the Rejection of Older Cardiac Transplants via Interleukin-17A', CIRCULATION, vol. 132, no. 2, pp. 122-31. https://doi.org/10.1161/CIRCULATIONAHA.114.014917

APA

Heinbokel, T., Oberhuber, R., Cetina Biefer, H. R., Boenisch, O., Hock, K., Bronson, R. T., Wilhelm, M. J., Iwakura, Y., Edtinger, K., Uehara, H., Quante, M., Voskuil, F., Krenzien, F., Slegtenhorst, B., Abdi, R., Pratschke, J., Elkhal, A., & Tullius, S. G. (2015). CD11c+ Dendritic Cells Accelerate the Rejection of Older Cardiac Transplants via Interleukin-17A. CIRCULATION, 132(2), 122-31. https://doi.org/10.1161/CIRCULATIONAHA.114.014917

Vancouver

Heinbokel T, Oberhuber R, Cetina Biefer HR, Boenisch O, Hock K, Bronson RT et al. CD11c+ Dendritic Cells Accelerate the Rejection of Older Cardiac Transplants via Interleukin-17A. CIRCULATION. 2015 Jul 14;132(2):122-31. https://doi.org/10.1161/CIRCULATIONAHA.114.014917

Bibtex

@article{b3cd49f545c14a2ea16dbf67d70b575e,
title = "CD11c+ Dendritic Cells Accelerate the Rejection of Older Cardiac Transplants via Interleukin-17A",
abstract = "BACKGROUND: Organ transplantation has seen an increased use of organs from older donors over the past decades in an attempt to meet the globally growing shortage of donor organs. However, inferior transplantation outcomes when older donor organs are used represent a growing challenge.METHODS AND RESULTS: Here, we characterize the impact of donor age on solid-organ transplantation using a murine cardiac transplantation model. We found a compromised graft survival when older hearts were used. Shorter graft survival of older hearts was independent of organ age per se, because chimeric young or old organs repopulated with young passenger leukocytes showed comparable survival times. Transplantation of older organs triggered more potent alloimmune responses via intragraft CD11c+ dendritic cells augmenting CD4+ and CD8+ T-cell proliferation and proinflammatory cytokine production, particularly that of interleukin-17A. Of note, depletion of donor CD11c+ dendritic cells before engraftment, neutralization of interleukin-17A, or transplantation of older hearts into IL-17A(-/-) mice delayed rejection and reduced alloimmune responses to levels observed when young hearts were transplanted.CONCLUSIONS: These results demonstrate a critical role of old donor CD11c+ dendritic cells in mounting age-dependent alloimmune responses with an augmented interleukin-17A response in recipient animals. Targeting interleukin-17A may serve as a novel therapeutic approach when older organs are transplanted.",
keywords = "Aging, Animals, Antigens, CD11c, Dendritic Cells, Graft Rejection, Heart Transplantation, Interleukin-17, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Knockout, Transplantation, Homologous",
author = "Timm Heinbokel and Rupert Oberhuber and {Cetina Biefer}, {Hector Rodriguez} and Olaf Boenisch and Karin Hock and Bronson, {Roderick T} and Wilhelm, {Markus J} and Yoichiro Iwakura and Karoline Edtinger and Hirofumi Uehara and Markus Quante and Floris Voskuil and Felix Krenzien and Bendix Slegtenhorst and Reza Abdi and Johann Pratschke and Abdallah Elkhal and Tullius, {Stefan G}",
note = "{\textcopyright} 2015 American Heart Association, Inc.",
year = "2015",
month = jul,
day = "14",
doi = "10.1161/CIRCULATIONAHA.114.014917",
language = "English",
volume = "132",
pages = "122--31",
journal = "CIRCULATION",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

RIS

TY - JOUR

T1 - CD11c+ Dendritic Cells Accelerate the Rejection of Older Cardiac Transplants via Interleukin-17A

AU - Heinbokel, Timm

AU - Oberhuber, Rupert

AU - Cetina Biefer, Hector Rodriguez

AU - Boenisch, Olaf

AU - Hock, Karin

AU - Bronson, Roderick T

AU - Wilhelm, Markus J

AU - Iwakura, Yoichiro

AU - Edtinger, Karoline

AU - Uehara, Hirofumi

AU - Quante, Markus

AU - Voskuil, Floris

AU - Krenzien, Felix

AU - Slegtenhorst, Bendix

AU - Abdi, Reza

AU - Pratschke, Johann

AU - Elkhal, Abdallah

AU - Tullius, Stefan G

N1 - © 2015 American Heart Association, Inc.

PY - 2015/7/14

Y1 - 2015/7/14

N2 - BACKGROUND: Organ transplantation has seen an increased use of organs from older donors over the past decades in an attempt to meet the globally growing shortage of donor organs. However, inferior transplantation outcomes when older donor organs are used represent a growing challenge.METHODS AND RESULTS: Here, we characterize the impact of donor age on solid-organ transplantation using a murine cardiac transplantation model. We found a compromised graft survival when older hearts were used. Shorter graft survival of older hearts was independent of organ age per se, because chimeric young or old organs repopulated with young passenger leukocytes showed comparable survival times. Transplantation of older organs triggered more potent alloimmune responses via intragraft CD11c+ dendritic cells augmenting CD4+ and CD8+ T-cell proliferation and proinflammatory cytokine production, particularly that of interleukin-17A. Of note, depletion of donor CD11c+ dendritic cells before engraftment, neutralization of interleukin-17A, or transplantation of older hearts into IL-17A(-/-) mice delayed rejection and reduced alloimmune responses to levels observed when young hearts were transplanted.CONCLUSIONS: These results demonstrate a critical role of old donor CD11c+ dendritic cells in mounting age-dependent alloimmune responses with an augmented interleukin-17A response in recipient animals. Targeting interleukin-17A may serve as a novel therapeutic approach when older organs are transplanted.

AB - BACKGROUND: Organ transplantation has seen an increased use of organs from older donors over the past decades in an attempt to meet the globally growing shortage of donor organs. However, inferior transplantation outcomes when older donor organs are used represent a growing challenge.METHODS AND RESULTS: Here, we characterize the impact of donor age on solid-organ transplantation using a murine cardiac transplantation model. We found a compromised graft survival when older hearts were used. Shorter graft survival of older hearts was independent of organ age per se, because chimeric young or old organs repopulated with young passenger leukocytes showed comparable survival times. Transplantation of older organs triggered more potent alloimmune responses via intragraft CD11c+ dendritic cells augmenting CD4+ and CD8+ T-cell proliferation and proinflammatory cytokine production, particularly that of interleukin-17A. Of note, depletion of donor CD11c+ dendritic cells before engraftment, neutralization of interleukin-17A, or transplantation of older hearts into IL-17A(-/-) mice delayed rejection and reduced alloimmune responses to levels observed when young hearts were transplanted.CONCLUSIONS: These results demonstrate a critical role of old donor CD11c+ dendritic cells in mounting age-dependent alloimmune responses with an augmented interleukin-17A response in recipient animals. Targeting interleukin-17A may serve as a novel therapeutic approach when older organs are transplanted.

KW - Aging

KW - Animals

KW - Antigens, CD11c

KW - Dendritic Cells

KW - Graft Rejection

KW - Heart Transplantation

KW - Interleukin-17

KW - Male

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Mice, Inbred DBA

KW - Mice, Knockout

KW - Transplantation, Homologous

U2 - 10.1161/CIRCULATIONAHA.114.014917

DO - 10.1161/CIRCULATIONAHA.114.014917

M3 - SCORING: Journal article

C2 - 25957225

VL - 132

SP - 122

EP - 131

JO - CIRCULATION

JF - CIRCULATION

SN - 0009-7322

IS - 2

ER -