Myeloid-Derived Suppressor Cells and Pulmonary Hypertension

Abstract

Myeloid–derived suppressor cells (MDSCs) comprised a heterogeneous subset of bone marrow–derived myeloid cells, best studied in cancer research, that are increasingly implicated in the pathogenesis of pulmonary vascular remodeling and the development of pulmonary hypertension. Stem cell transplantation represents one extreme interventional strategy for ablating the myeloid compartment but poses a number of translational challenges. There remains an outstanding need for additional therapeutic targets to impact MDSC function, including the potential to alter interactions with innate and adaptive immune subsets, or alternatively, alter trafficking receptors, metabolic pathways, and transcription factor signaling with readily available and safe drugs. In this review, we summarize the current literature on the role of myeloid cells in the development of pulmonary hypertension, first in pulmonary circulation changes associated with myelodysplastic syndromes, and then by examining intrinsic myeloid cell changes that contribute to disease progression in pulmonary hypertension. We then outline several tractable targets and pathways relevant to pulmonary hypertension via MDSC regulation. Identifying these MDSC-regulated effectors is part of an ongoing effort to impact the field of pulmonary hypertension research through identification of myeloid compartment-specific therapeutic applications in the treatment of pulmonary vasculopathies.

The Third Man: DNA sensing as espionage in pulmonary vascular health and disease

“…Bone marrow-derived cells have previously been described to play unique roles in development of pulmonary vascular disease. 109 Related, cytosolic DNA sensing through cGAS/STING signaling is known to tightly regulate the innate immune response preventing development of chronic inflammatory disorders. 110 For example, plasmacytoid dendritic cells-a unique DC sub-population that specializes in interferon production-have been described to increase interferon signaling primarily through cGAS/ STING activation.…”

Myeloid-derived suppressor cells and pulmonary hypertension

“…In the past, most studies focus on macrophages, neutrophils, and DCs, to explore inflammatory microenvironment ( 33 – 35 ). Nowadays, more and more studies suggest that MDSCs could also play an important role in inflammatory microenvironment ( 17 , 36 – 38 ). Under physiological conditions, MDSCs are important immune cells for hematopoietic stem cells to maintain homeostasis ( 39 ).…”

“…Under physiological conditions, MDSCs are important immune cells for hematopoietic stem cells to maintain homeostasis ( 39 ). Under pathological conditions, recruitment of MDSCs from circulating blood to the outer membrane of pulmonary artery may be an important mechanism for PVR and PH progression ( 17 , 38 ). Thus, there is an imperative need to explore MDSCs in PH, and targeting MDSCs may provide clinical guidance for the treatment of PH.…”

“…Group 3 PH is associated with lung diseases and/or hypoxia, and it is found the MDSCs are dominated by PMN-MDSCs, which exert the immune suppressive function through Arg1 and ROS ( 36 , 37 , 40 ). It is suggested that MDSCs are important constituents of immune microenvironment with a pivotal role in PH progression ( 38 ). Next, we focus on the chemokines, cytokines, T cells, NK cells and molecular mechanisms to explore the immune-regulatory functions of MDSCs in PH, which may provide us with new strategy for treatment of PH.…”

Vanillic Acid Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension by Enhancing NO Signaling Pathways

“…11 The beneficial effect of arginase inhibition has been demonstrated in pulmonary hypertension. [12][13][14] Vanillic acid (VA) is a phenolic compound that is widely distributed in edible plants and fruits. 15,16 It has been associated with a variety of pharmacological activities, including antioxidant, antihypotensive, cardioprotective, hepatoprotective, and antiapoptotic.…”