CD14highCD16+ monocytes are the main producers of Interleukin-10 following clinical heart transplantation

Kristina Ludwig; Evgeny Chichelnitskiy; Jenny F Kühne; Bettina Wiegmann; Jasper Iske; Nadine Ledwoch; Fabio Ius; Kerstin Beushausen; Jana Keil; Susanne Iordanidis; Sebastian V Rojas; Jawad Salman; Ann-Kathrin Knoefel; Axel Haverich; Gregor Warnecke; Christine S Falk

doi:10.3389/fimmu.2023.1257526

CD14^highCD16⁺ monocytes are the main producers of Interleukin-10 following clinical heart transplantation

Front Immunol. 2023 Oct 23:14:1257526. doi: 10.3389/fimmu.2023.1257526. eCollection 2023.

Authors

Kristina Ludwig^{1

2}, Evgeny Chichelnitskiy¹, Jenny F Kühne¹, Bettina Wiegmann^{3

4

5}, Jasper Iske^{1

6}, Nadine Ledwoch¹, Fabio Ius^{3

5}, Kerstin Beushausen¹, Jana Keil¹, Susanne Iordanidis¹, Sebastian V Rojas⁷, Jawad Salman³, Ann-Kathrin Knoefel³, Axel Haverich³, Gregor Warnecke⁸, Christine S Falk^{1

5

9}

Affiliations

¹ Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany.
² Department of Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
³ Department for Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
⁴ Lower Saxony Center for Biomedical Engineering, Implant Research and Development, Hannover Medical School, Hannover, Germany.
⁵ DZL, German Center for Lung Diseases, BREATH site, Hannover, Germany.
⁶ Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum der Charité, Berlin, Germany.
⁷ Heart and Diabetes Center Nordrhein-Westfalen, University Hospital Ruhr-University Bochum, Bad Oeynhausen, Germany.
⁸ Department of Cardiac Surgery, University Hospital Heidelberg, Heidelberg, Germany.
⁹ DZIF, German Center for Infection Research, TTU-IICH, Hannover, Germany.

Abstract

Introduction: Following heart transplantation, a cascade of immunological responses is initiated influencing the clinical outcome and long-term survival of the transplanted patients. The anti-inflammatory cytokine interleukin-10 (IL-10) was shown to be elevated in the blood of heart transplant recipients directly after transplantation but the releasing cell populations and the composition of lymphocyte subsets following transplantation have not been thoroughly studied.

Methods: We identified immune cells by immunophenotyping and analyzed intracellular IL-10 production in peripheral blood mononuclear cells (PBMC) of heart transplanted patients (n= 17) before, directly after and 24h post heart transplantation. The cells were stimulated with lipopolysaccharide or PMA/Ionomycin to enhance cytokine production within leukocytes in vitro.

Results and discussion: We demonstrate that intermediate monocytes (CD14^highCD16⁺), but not CD8⁺ T cells, CD4⁺ T cells, CD56⁺ NK cells or CD20⁺ B cells appeared to be the major IL-10 producers within patients PBMC following heart transplantation. Consequently, the absolute monocyte count and the ratio of intermediate monocytes to classical monocytes (CD14⁺CD16^-) were specifically increased in comparison to pre transplant levels. Hence, this population of monocytes, which has not been in the focus of heart transplantation so far, may be an important modulator of clinical outcome and long-term survival of heart transplant recipients. Alteration of blood-circulating monocytes towards a CD14^highCD16⁺ phenotype could therefore shift the pro-inflammatory immune response towards induction of graft tolerance, and may pave the way for the optimization of immunosuppression.

Keywords: heart transplantation; interleukin-10; ischemia-reperfusion injury; monocytes; organ transplantation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cytokines
Heart Transplantation*
Humans
Interleukin-10
Leukocytes, Mononuclear
Lipopolysaccharide Receptors
Monocytes*
Receptors, IgG

Substances

Interleukin-10
Lipopolysaccharide Receptors
Receptors, IgG
Cytokines

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This project was supported by the German Research Foundation DFG, SFB738 project B3, and FA-483/1-1, the German Center for Infection Research DZIF TTU-IICH, and the MHH Transplant Center project 19_09.