Abstract
Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immune cells from the myeloid lineage. MDSCs expand in pathological situations, such as chronic infection, cancer, autoimmunity, and allograft rejection. As chronic lung allograft dysfunction (CLAD) limits long-term survival after lung transplantation (LTx), MDSCs may play a role in its pathophysiology. We assessed phenotype and frequency of MDSCs in peripheral blood from lung transplant recipients and its relationship to post-transplant complications and immunosuppression. Granulocytic (G)-MDSC were identified and quantified by flow cytometry of blood from 4 control subjects and 20 lung transplant patients (stable n = 6, infection n = 5; CLAD n = 9). G-MDSC functionality was assessed in vitro by their capability to block CD4 and CD8 T cell proliferation. More G-MDSC could be assessed using EDTA tubes compared to heparin tubes (p = 0.004). G-MDSC were increased in stable lung transplant recipients vs. non-transplant controls (52.1% vs. 9.4%; p = 0.0095). The infection or CLAD groups had lower G-MDSCs vs. stable recipients (28.2%p = 0.041 and 33.0%; p = 0.088, respectively), but were not different among CLAD phenotypes. G-MDSC tended to correlate with cyclosporine A and tacrolimus levels (r2 = 0.18; r2 = 0.17). CD4 and CD8 cells proliferation decreased by 50 and 80% if co-cultured with MDSCs (1:6 and 1:2 MDSC:T-cell ratio, respectively). In conclusion, circulating MDSCs are measurable, functional and have a G-MDSC phenotype in lung transplant patients. Their frequency is increased in stable patients, decreased during post-transplant complications, and related to level of immunosuppression. This study may pave the way for further investigations of MDSC in the context of lung transplantation.
Highlights
From a transplant immunological point of view, graft acceptance is the fundamental element in allograft survival
Myeloid-derived suppressor cells (MDSC) were evaluated in lung transplant recipients and granulocytic MDSCs (G-MDSCs) (CD33+/CD66b+) could be identified in the lowdensity fraction of peripheral blood mononuclear cells (PBMCs)
MDSCs are known for their role in immune regulation and allograft acceptance, and are involved in delayed graft rejection [17, 24, 25]
Summary
From a transplant immunological point of view, graft acceptance is the fundamental element in allograft survival. Upregulation of ARG1, NO, and ROS are key mechanism to suppress T cell proliferation [9] and the production of IFNγ [10] Another hallmark is the upregulation of the transcription factor signal transducer and activator of transcription 3 (STAT3). STAT3, which functions as a signaling hub, integrating the different cues of the immunologic micro-environment [11, 12] regulates the expansion of MDSCs by stimulating myelopoiesis and inhibiting myeloid-cell differentiation. It promotes MDSC survival by inducing the expression of cyclin D1, B-cell lymphoma XL (BCL-XL) and MYC [4]. To assess if MDSCs can serve as a potential new research target in the field of lung transplantation since chronic lung allograft dysfunction (CLAD), considered to be driven by an overactive T cell response, remains the most important factor limiting long-term survival after transplantation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
