Myeloid-Derived Suppressor Cells at the Intersection of Inflammaging and Bone Fragility

Abstract

Age-related alteration of the immune system with aging, or immunosenescence, plays a major role in several age-associated conditions, including loss of bone integrity. Studies over the past several years have clearly established the immune system is chronically activated with advanced aging, termed inflammaging, and is characterized by elevated levels of proinflammatory cytokines in response to physiological or environmental cues that essentially result in an arrested immune system that maintains a low-level state of activation. This age-associated inflammation impacts several biological systems including the innate immune system, where aging results in a skewing of the hematopoiesis towards the myeloid lineage, including the expansion of myeloid-derived suppressor cells (MDSCs). This heterogeneous population of myeloid cells classically displays immunosuppressive capacity but they also have the ability to directly differentiate into osteoclasts. This review explores the possibility of inflammaging to be involved in reduction of bone microarchitecture and loss of bone mass/strength through the expansion of MDSCs and the osteoclastogenic capacity and activity.

Myeloid‐derived suppressor cells in obesity‐associated periodontal disease: A conceptual model

“…We provide the first evidence suggesting that when myeloid‐derived suppressor cell populations are expanded with simultaneous suppression of T‐cell and B‐cell populations, there is spontaneous alveolar bone loss 60 . In addition, we have shown that monocytic myeloid‐derived suppressor cells (CD11b + Ly6C hi Ly6G) possess cellular plasticity by virtue of their ability to form mature osteoclasts 62 . In this conceptual perspective, we offer a novel “two‐hit” model to explain obesity‐exacerbated alveolar bone destruction.…”

Multitasking by the OC Lineage during Bone Infection: Bone Resorption, Immune Modulation, and Microbial Niche

“…MDSCs are expanded and activated by a number of pro-inflammatory and infectious stimuli and inhibit T cells and innate immune functions of other myeloid cells via release of ROS, NO, and enzymes such as arginase-1 [ 71 ]. Several groups have shown that MDSCs can also differentiate into OCs and contribute to bone erosion in various noninfectious models [ 72 , 73 , 74 , 75 ], so they likely have the potential to cause tissue damage in iOM ( Figure 2 ). In mouse models of prosthetic-associated S. aureus biofilms, MDSCs have been shown to accumulate at higher rates than neutrophils and macrophages, but their role in disease progression is likely complex.…”

Discovering Myeloid Cell Heterogeneity in Mandibular Bone – Cell by Cell Analysis

“…And the prolonged and marked expansion of the IMCs lead to the expansion of MDSC population (Gabrilovich and Nagaraj, 2009). Several reports support MDSC plasticity as osteoclast progenitors under various pathological conditions associated with bone destruction (Sawant et al, 2013;Zhang et al, 2015;Kirkwood et al, 2018). Therefore, to study whether the specificity of mandibular bone is due to the heterogeneity of bone marrow cells, it is necessary to explore not only the populations of lineage committed bone marrow cells but also their progenitors.…”