Neutrophils and polymorphonucler myeloid-derived suppressor cells (PMN-MDSC) share origin and many morphological and phenotypic features. However, they have different biological role. Neutrophils are one of the major mechanisms of protection against invading pathogens, whereas PMN-MDSC have immune suppressive activity and restrict immune responses in cancer, chronic infectious disease, trauma, sepsis, and many other pathological conditions. Although in healthy adult individuals, PMN-MDSC are not or barely detectable, in patients with cancer and many other diseases they accumulate at various degree and co-exist with neutrophils. Recent advances allow for better distinction of these cells and better understanding of their biological role. Accumulating evidence indicates PMN-MDSC as pathologically activated neutrophils, with important role in regulation of immune responses. In this review, we provide an overview on the definition and characterization of PMN-MDSC and neutrophils, their pathological significance in a variety of diseases, and their interaction with other stromal components.

Group 2 innate lymphoid cells (ILC2s) are emerging as key players in the pathogenesis of allergic airway inflammation. The mechanisms regulating ILC2, however, are not fully understood. Here, we found that ICAM-1 is required for the development and function of ILC2. ICAM-1-deficient ( ) mice displayed significantly lower levels of ILC2s in the bone marrow and peripheral tissues than wild-type controls. CLP transfer and in vitro culture assays revealed that the regulation of ILC2 by ICAM-1 is cell intrinsic. Furthermore, ILC2s from mice were functionally impaired, as indicated by the diminished production of type-2 cytokines in response to IL-33 challenge. The reduction in lung ILC2s caused a clear remission of airway inflammation in mice after administration of papain or We further demonstrate that ILC2 defects caused by ICAM-1 deficiency are due to ERK signaling-dependent down-regulation of GATA3 protein. Collectively, these observations identify ICAM-1 as a novel regulator of ILC2.

Statins, widely prescribed as cholesterol-lowering drugs, have recently been extensively studied for their pleiotropic effects on immune systems, especially their beneficial effects on autoimmune and inflammatory disorders. However, the mechanism of statin-induced immunosuppression is far from understood. Here, we found that atorvastatin promoted the expansion of myeloid-derived suppressor cells (MDSCs) both in vitro and in vivo. Atorvastatin-derived MDSCs suppressed T-cell responses by nitric oxide production. Addition of mevalonate, a downstream metabolite of 3-hydroxy-3-methylglutaryl coenzyme A reductase, almost completely abrogated the effect of atorvastatin on MDSCs, indicating that the mevalonate pathway was involved. Along with the amelioration of dextran sodium sulphate (DSS) -induced murine acute and chronic colitis, we observed a higher MDSC level both in spleen and intestine tissue compared with that from DSS control mice. More importantly, transfer of atorvastatin-derived MDSCs attenuated DSS acute colitis and T-cell transfer of chronic colitis. Hence, our data suggest that the expansion of MDSCs induced by statins may exert a beneficial effect on autoimmune diseases. In summary, our study provides a novel potential mechanism for statins-based treatment in inflammatory bowel disease and perhaps other autoimmune diseases.

Myeloid Derived Suppressor Cell (MDSC) has been raised to be a novel target for multiple cancers. However, target agents on MDSC have not display promising efficacy. One of the critical reasons shall be less optimal patient selection. In the present study, we aimed to identify clinical parameters relevant to MDSC level in hepatocellular carcinoma (HCC) patients for future MDSC targeted therapy. In the present study, a series of 55 HCC patients (testing group) and 20 healthy donors were analyzed investigating frequencies of MDSC in peripheral blood mononuclear cells (PBMC). As a result, we found that MDSC level was increased in HCC patients compared to healthy donors (10.33% vs 1.54%, p < 0.0001). The monocytes (r2 = 0.2875, p < 0.0001), neutrophils (r2 = 0.3630, p < 0.0001) and platelet counts (r2 = 0.0828, p = 0.0331) in circulation was positively associated with MDSC level. Then, the prognostic value of the above predictors was determined in a retrospective database of 255 HCC patients (validation group). The baseline characteristics of testing and validation group were similar. Multivariate analysis by Cox regression revealed that neutrophil count was an independent predictor for overall survival (OS) (p = 0.000, HR 1.065, 95% CI 1.028–1.103), with the rest parameters failed to reach a significant result. In summary, the present study firstly identified blood neutrophil counts was a predictor of MDSC level in PBMC for HCC patients. And, patients with higher neutrophil count level might be the optimal patient subgroup for MDSC targeted therapy.