Myeloid-Derived Suppressor Cells in Patients With Acute Pancreatitis With Increased Inhibitory Function

Abstract

Acute pancreatitis (AP) is pancreatic or systemic inflammation without or with motion organ dysfunction. Severe acute pancreatitis (SAP) is the main cause of death for patients with AP. A pro-/anti-inflammatory imbalance is considered the key regulation of disease severity. However, the real mechanism of SAP remains unclear. This study aimed to identify the frequency and specific roll of myeloid-derived suppressor cell (MDSC) in AP. We evaluated MDSC frequency and disease severity by analyzing MDSCs in the peripheral blood of healthy controls (HCs) and patients with mild acute pancreatitis (MAP) and SAP by flow cytometry. We also compared the frequency and inhibitory ability of MDSCs from HCs and SAP, and finally detected the reason for the difference in inhibitory ability. AP was marked by expansion of MDSCs as well as its subsets, granulocytic MDSCs (G-MDSCs) and monocytic MDSCs (M-MDSCs). The proportion of MDSC in the peripheral blood mononuclear cells of patients with AP was increased and positively correlated with AP severity. The frequency of MDSC was decreased after treatment compared with pre-treatment. CD3+ T cells were remarkably inhibited by MDSC derived from the patients with SAP. In the expression of arginase-1 (Arg-1) and reactive oxygen species (ROS), the MDSCs from patients with SAP increased. These findings demonstrated that MDSCs expanded in the peripheral blood in patients with AP, especially in those with SAP. Moreover, the inhibitory ability of MDSCs was increased in the patients with SAP compared with that in the HCs. The enhanced suppressive function was possibly caused by an overexpression of Arg-1 and ROS.

Exploring the potential immune cells related to the heredity of acute pancreatitis based on Mendelian randomization study

“…A large number of studies have shown that a variety of immune cells are involved during the onset of AP, and the imbalance between pro-in ammatory and anti-in ammatory immune systems is an important mechanism that promotes disease progression [8][9][10][11] .However, the relationship at the genetic level is still unclear, so we used MR analysis and based on a large amount of public genetic data found that AP has signi cant causal effects on four types of immune cells, CD14 + CD16-, CD28, CD14+, and Mo MDSC AC. (P < 0.05), these results indicate that immune cells may be an important factor in uencing AP, and also mean that immune cells at the genetic level play an important role in the pathogenesis of AP.…”

Monocytic HLA-DR Expression in Immune Responses of Acute Pancreatitis and COVID-19

“…A proportion of circulating HLA-DR −/low monocytes seen in both AP and COVID-19 patients have been identified as CD14 + CD11b + HLA-DR −/low CD15 − monocytic myeloid-derived suppressor cells (M-MDSCs); these cell types may cloud earlier studies on the topic, as they could be misidentified as HLA-DR −/low classical monocytes [ 174 , 175 , 176 ]. M-MDSCs are characterized by their potent immunosuppressive effects on other immune cells, especially T cells, through various mechanisms including secretion of arginase-1 (Arg-1), and inducible nitric oxide synthase, production of reactive oxygen and nitrogen species, secretion of cytokines including TGF-β and IL-10, and induction of regulatory T cells [ 175 ].…”

“…The proportion of M-MDSCs in peripheral blood mononuclear cells correlates with AP severity as reflected by plasma CRP levels, APACHE II score, and length of stay [ 174 ]. Increased levels of Arg-1 and ROS can further be observed in AP patients, especially those with a severe clinical course [ 174 ].…”

“…The proportion of M-MDSCs in peripheral blood mononuclear cells correlates with AP severity as reflected by plasma CRP levels, APACHE II score, and length of stay [ 174 ]. Increased levels of Arg-1 and ROS can further be observed in AP patients, especially those with a severe clinical course [ 174 ]. Similarly, expansion of M-MDSCs was reported together with increased Arg-1 activity in plasma, and these are associated with severity and fatal outcome in COVID-19 patients [ 175 ].…”

Targeted drug delivery system for ovarian cancer microenvironment: Improving the effects of immunotherapy

“…When activated and accumulating in peripheral lymphoid tissues and the tumors, they are implicated in suppressing immunity and promoting tumor progression. The different function and differentiation of MDSCs are related to the different phenotype of the TME ( 18 ).…”