CXCR4 blockade reduces the severity of murine heart allograft rejection by plasmacytoid dendritic cell-mediated immune regulation

Fu J, Lehmann C, Wang X, Wahlbuhl M, Allabauer I, Wilde B, Amon L, Dolff S, Cesnjevar R, Kribben A, Wölfle J, Rascher W, Hoyer PF, Dudziak D, Witzke O, Hörning A (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 11

Article Number: 23815

Journal Issue: 1

DOI: 10.1038/s41598-021-03115-z

Abstract

Allograft-specific regulatory T cells (Treg cells) are crucial for long-term graft acceptance after transplantation. Although adoptive Treg cell transfer has been proposed, major challenges include graft-specificity and stability. Thus, there is an unmet need for the direct induction of graft-specific Treg cells. We hypothesized a synergism of the immunotolerogenic effects of rapamycin (mTOR inhibition) and plerixafor (CXCR4 antagonist) for Treg cell induction. Thus, we performed fully-mismatched heart transplantations and found combination treatment to result in prolonged allograft survival. Moreover, fibrosis and myocyte lesions were reduced. Although less CD3+ T cell infiltrated, higher Treg cell numbers were observed. Noteworthy, this was accompanied by a plerixafor-dependent plasmacytoid dendritic cells-(pDCs)-mobilization. Furthermore, in vivo pDC-depletion abrogated the plerixafor-mediated Treg cell number increase and reduced allograft survival. Our pharmacological approach allowed to increase Treg cell numbers due to pDC-mediated immune regulation. Therefore pDCs can be an attractive immunotherapeutic target in addition to plerixafor treatment.

Authors with CRIS profile

Christian Lehmann Department of Dermatology Mandy Wahlbuhl-Becker Department of Paediatrics and Adolescent Medicine Lukas Amon Department of Dermatology Robert Cesnjevar Department of Paediatric Cardiac Surgery Joachim Wölfle Lehrstuhl für Kinder- und Jugendmedizin Wolfgang Rascher Department of Paediatrics and Adolescent Medicine Diana Dudziak Professur für die Biologie Dendritischer Zellen André Hörning Department of Paediatrics and Adolescent Medicine

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung (IZKF)

Related research project(s)

A080: Control of immune responses by inflammasomes in primary dendritic cells Jan. 1, 2020 - Dec. 31, 2022

Involved external institutions

Universität Duisburg-Essen (UDE) DE Germany (DE)

How to cite

APA:

Fu, J., Lehmann, C., Wang, X., Wahlbuhl, M., Allabauer, I., Wilde, B.,... Hörning, A. (2021). CXCR4 blockade reduces the severity of murine heart allograft rejection by plasmacytoid dendritic cell-mediated immune regulation. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-03115-z

MLA:

Fu, Jian, et al. "CXCR4 blockade reduces the severity of murine heart allograft rejection by plasmacytoid dendritic cell-mediated immune regulation." Scientific Reports 11.1 (2021).

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