Neutrophils have long been considered as cells playing a crucial role in the immune defence against invading pathogens. Accumulating evidence strongly supported the direct and indirect regulatory effects of neutrophils on adaptive immunity. Exogenous cytokines or cytokines produced in an autocrine manner as well as a cell-to-cell contact between neutrophils and T cells could induce the expression of MHC-II and costimulatory molecules on neutrophils, supporting that neutrophils may function as antigen-presenting cells (APCs) in respects of presenting antigens and activating T cells. In addition to the inflammatory roles, neutrophils also have the propensity and ability to suppress the immune response through different mechanisms. In this review, we will mainly highlight the heterogeneity and functional plasticity of neutrophils and the antigen-presenting capacity of different neutrophil subsets. We also discuss mechanisms relevant to the regulatory effects of neutrophils on adaptive immunity. Understanding how neutrophils modulate adaptive immunity may provide novel strategies and new therapeutic approaches for diseases associated with neutrophils.Graphical

The thymus is the primary immune organ responsible for generating self‐tolerant and immunocompetent T cells. However, the thymus gradually involutes during early life resulting in declined naïve T‐cell production, a process known as age‐related thymic involution. Thymic involution has many negative impacts on immune function including reduced pathogen resistance, high autoimmunity incidence, and attenuated tumor immunosurveillance. Age‐related thymic involution leads to a gradual reduction in thymic cellularity and thymic stromal microenvironment disruption, including loss of definite cortical‐medullary junctions, reduction of cortical thymic epithelial cells and medullary thymic epithelial cells, fibroblast expansion, and an increase in perivascular space. The compromised thymic microenvironment in aged individuals substantially disturbs thymocyte development and differentiation. Age‐related thymic involution is regulated by many transcription factors, micro RNAs, growth factors, cytokines, and other factors. In this review, we summarize the current understanding of age‐related thymic involution mechanisms and effects.

CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) are an important population of innate regulatory cells mainly comprising monocytic MDSCs (M-MDSCs) with a phenotype of CD11b+Ly6G−Ly6Chigh and granulocytic MDSCs (G-MDSCs) with a phenotype of CD11b+Ly6G+Ly6Clow in mice. They play crucial roles in the pathogenesis of cancers, chronic infections, autoimmune diseases, and transplantation. Various extracellular factors such as lipopolysaccharide (LPS), macrophage colony-stimulating factor (M-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), interleukin (IL)-6, interferon gamma (IFNγ), IL-1β, vascular endothelial growth factor (VEGF), Hsp72, IL-13, C5a, and prostaglandin E2 (PGE2) can induce MDSC differentiation, whereas IL-4 and all-trans-retinoic acid can inhibit this process. For the intracellular signals, signal transducer and activator of transcription (STAT) family members, C/EBPβ and cyclooxigenase-2 (COX-2) promote MDSC function, whereas interferon regulatory factor-8 (IRF-8) and Smad3 downregulate MDSC activity. The immunosuppressive function of MDSCs is mediated through various effector molecules, primarily cellular metabolism-related molecules such as nitric oxide (NO), arginase, reactive oxygen species (ROS), transforming growth factor β (TGFβ), IL-10, indoleamine 2,3-dioxygenase (IDO), heme oxygenase-1 (HO-1), carbon monoxide (CO), and PGE2. In this article, we will summarize the molecules involved in the induction and function of MDSCs as well as the regulatory pathways of MDSCs.