B-1a cells represent a distinct B cell population with unique phenotype, self-renewing capacity and restricted Igμ repertoire. They primarily locate in body cavity and also exist in spleen. The different subpopulations of B-1a cells are heavily affected by local environment. Our previous studies revealed that MARVEL-domain-containing membrane protein, CMTM7, was involved in B-1a cell development. Here

While T cells play a critical role in protective immunity against infection, they are also responsible for graft rejection in the setting of transplantation. T cell differentiation is regulated by both intrinsic transcriptional pathways as well as extrinsic factors such as antigen encounter and the cytokine milieu. Herein, we review recent discoveries in the transcriptional regulation of T cell differentiation

Asthma is an inflammatory disease of the airways and numerous cytokines contribute to this pathogenesis. It is shown that challenge of airways with IL-33 induces asthma-like pathological changes in mice, but the possible downstream cytokines in this process remain to be characterised. To explore this, we compared changes in the airways of wildtype (WT) and IL-9 deficient mice challenged with IL-33

Nonhuman primates (NHP) are important pre-clinical models for evaluation of the safety and efficacy of the most promising potential therapeutic advances in organ transplantation based on rodent studies. Although rare, dendritic cells (DC) play important roles in preservation of self tolerance and DC with immunoregulatory properties (regulatory DC; DCreg) can promote transplant tolerance in rodents

Optical imaging is a valuable tool to visualise biological processes in the context of the tissue. Each imaging modality provides the biologist with different types of information – cell dynamics and migration over time can be tracked with time-lapse imaging (e.g. intra-vital imaging); an overview of whole tissues can be acquired using optical clearing in conjunction with light sheet microscopy; finer

Pattern recognition receptors (PRRs) are germline-encoded sensors best characterized for their critical role in host defense. However, there is accumulating evidence that organ transplantation induces the release or display of molecular patterns of cellular injury and death that trigger PRR-mediated inflammatory responses. There are also new insights that indicate PRRs are able to distinguish between

Asthma is a heterogeneous chronic inflammatory disease due to immune disorder, in which the activated T cells are predominantly of the T-helper 2 (Th2) cytokine phenotype. Previous studies have shown that Group 2 innate lymphoid cells (ILC2s) and IL-9 are associated with Th2-mediated immune-inflammatory injury in asthma. However, the relationship between ILC2s and IL-9 and the immunopathological mechanism

AIMS To investigate whether placenta-derived mesenchymal stromal cells (hPMSCs) have immunoregulatory effects on PD-1+ T cell generation by controlling ROS production and thus alleviating GVHD. MAIN METHODS Flow cytometry was used to analyze the percentage of PD-1+ T cells, as well as the generation of ROS, GSH and GST in PD-1+ T cells. The expression of GST in the spleen and liver was analyzed by

Toll-like receptor (TLR) 2/1 signalling is linked to autophagy through transcriptional actions of the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-vitamin D receptor (VDR) complex. Population-specific effects have been reported for TLR2/1-VDR signalling. We hypothesized that population effects extend to autophagy and are influenced by vitamin D status. Serum 25(OH)D3 of healthy South Africans (Black individuals

Mice that express a single transgenic T cell receptor have a low incidence of T cell lymphoma development. We investigated whether this tumor development is restricted by surveillance mechanisms that are exerted by IL-15-dependent cells. Lymphoma incidence was increased to between 30 and 60% when TCR transgenes were expressed in IL-15-deficient mice. Mice in which NK cells had been depleted genetically

The gastrointestinal (GI) tract microbiota is an environmental factor that regulates host immunity in allo-transplantation (allo-Tx). It is required for the development of resistance against pathogens and the stabilization of mucosa-associated lymphoid tissue. The gut-microbiota axis may also precipitate allograft rejection by producing metabolites that activate host cell-mediated and humoral immunity

Mast cells (MCs) are engaged in host defense against various pathogens as they are equipped with pattern recognition receptors (PRRs). Among PRRs expressed on MCs, there are also molecules recognizing components of the fungal cell wall, which are able to induce cellular activation and response. However, little information is available concerning the MC activation by various fungal-derived components

B7-H3 as a newly identified costimulatory molecule that belongs to B7 ligand family, is broadly expressed in both lymphoid and non-lymphoid tissues. The overexpression of B7-H3 has been verified to be correlated with the poor prognosis and poor clinical outcome of several human cancers. In recent years, researchers reveal that B7-H3 is involved in the pathogenesis of various autoimmune diseases, such

We delineated the expression of DAP12 (DNAX-Activating Protein) and its associated receptors, TREM-1, TREM-2 and MDL-1 in pig alveolar monocyte/macrophages (AMM) that have attained M1 or M2 phenotypes. Pig AMM stimulated in vitro with IFN-γ and IL-4 induced the expression of M1 (TNFα and iNOS) and M2 (ARG1 and no MMR) phenotypic markers, respectively. In influenza infected pigs at seven days post-infection

Chimeric antigen receptors (CAR) utilize costimulatory domains to enhance anti-tumor efficacy. However, it is unclear which costimulatory domain is preferable. Therefore, the intracellular domains of CD28, Dap10, 41BB, GITR, ICOS, or OX40 were compared in a murine chimeric PD1 (chPD1) receptor that targets tumor-associated PD1 ligands. Upon antigen restimulation, T cells expressing chPD1-CD28 receptors

Human rhinovirus (hRV) is the most common cause of asthma exacerbation characterized by clinical and pathophysiological heterogeneity. Steroid-sensitive, Th2 type-eosinophilic asthma has been somewhat studied, but hRV-induced neutrophilic asthma exacerbation is poorly understood. Here, CCR5 was found to play a role in attenuating neutrophilic airway inflammation in hRV-induced asthma exacerbation using

Cellular metabolism is central to T cell function and proliferation, with most of the research to date focusing on cancer and autoimmunity. Cellular metabolism is associated with a host of physiological phenomena, from epigenetic changes, to cellular function and fate. For the purpose of this review, we will discuss the metabolism of T cells relating to their differentiation and function. We will cover

Many aspects remain elusive of the mechanisms governing T cell quiescence. Here we show that E protein activity helps to establish a quiescent program in naïve T cells. Decreased E protein activity, as the consequence of enforced expression of an Id1 transgene, led to the accumulation of CD4+CD44hi T cells. The naïve CD4+ T cells from this transgenic strain mounted a vigorous proliferative response

Extracellular vesicles (EVs), including exosomes, ectosomes and apoptotic vesicles, play an essential role in communication between cells of the innate and adaptive immune systems. Recent studies showed that EVs released after transplantation of allogeneic tissues and organs are involved in the immune recognition and response leading to rejection or tolerance in mice. After skin, pancreatic islet,

The shift of emphasis from short-term to long-term graft outcomes has led to renewed interests in how the innate immune cells regulate transplant survival, an area that is traditionally dominated by T cells in the adaptive system. This shift is driven largely by the limited efficacy of current immunosuppression protocols which primarily target T cells in preventing chronic graft loss, as well as by

Transplantation of fully allogeneic organs into immunocompetent recipients invariably elicits T cell and B cell responses that lead to the production of donor-specific antibodies (DSA). When immunosuppression is inadequate donor-specific T cell and B cell responses escape, leading to T cell-mediated rejection (TCMR), antibody mediated (ABMR) rejection, or mixed rejection (MR) exhibiting features of

AIMS Non-enzymatic reaction of biomolecules leads to the formation of advanced glycation end products (AGEs). AGEs plays significant role in the pathophysiology of type 2 diabetes mellitus. Methylglyoxal (MG) is a highly reactive carbonyl compound which causes formation of early (ketoamines), intermediate (dicarbonyls) and advanced glycation end products (AGEs). Glycation also results in the generation

NFAT2 activity was shown to be of critical importance in B cell receptor signaling, development and proliferation; however its role in B cell development in the periphery is still not completely understood. We confirmed that NFAT2 deletion leads to impaired B1 B cell development, supported by our finding of limited B1 progenitors in the bone marrow and spleen of NFAT2 deficient mice. Moreover, we show

Pathogenic microorganisms utilize multiple approaches to break down host immunity in favor of their invasion, of which, cystatin C is one of the soluble factors secreted by parasites reported to affect host immunity in vivo. The cellular targets and mechanisms of action in vivo of cystatin C, however, are far from clear. As professional antigen-presenting cells, dendritic cells (DCs) are first immune

Type I Interferon (IFN) signaling plays a critical role in dendritic cell (DC) development and functions. Inhibition of hyper type I IFN signaling promotes cDC2 subtype development. Relb is essential to development of cDC2 subtype and here we analyzed its effect on type I IFN signaling in DCs. We show that Relb suppresses the homeostatic type I IFN signaling in cDC2 cultures. TLR stimulation of FL-DCs

The polarization of macrophages is critical to inflammation and tissue repair, with unbalanced macrophage polarization associated with critical dysfunctions of the immune system. Cytochrome P450 1A1 (CYP1A1) is a hydroxylase mainly controlled by the inflammation-limiting aryl hydrocarbon receptor (AhR), which plays a critical role in mycoplasma infection, oxidative stress injury, and cancer. Arginase-1

Uncontrolled activation of NLRP3 inflammasome initiates a series of human inflammatory diseases. Targeting NLRP3 inflammasome has attracted considerable attention in developing potential therapeutic interventions. Here, we reported that dehydrocostus lactone (DCL), a main component of Saussurea lappa from the traditional Chinese medicine, inhibited NLRP3 inflammasome-mediated caspase-1 activation and

We recently reported that Tregs from long-term Belatacept-treated kidney transplant patients displayed an altered phenotype and impaired suppressive function compared to Tregs from healthy controls. However, it remains unknown whether ex vivo expansion of Tregs from patients who underwent long-term immunosuppression may be feasible to be used in their treatment. In this work, Tregs from Belatacept-treated

Chimeric antigen receptor (CAR)-modified T cell therapy evokes only modest antitumor responses in solid tumors. Meso-CAR-T cells are CAR-T cells targeted mesothelin, which are over-expressed in tumor tissues of breast cancer patients. To improve the therapeutic effects, we combined it with rAd.sT, a transforming growth factor β signaling-targeted oncolytic adenovirus, to therapy breast cancer. In subcutaneous

Tissue plasminogen activator (tPA), a component of the plasminogen activator (PA) system, is elevated in inflammatory neurological disorders. In the present study, we explored the immunomodulatory activity of tPA in experimental autoimmune encephalomyelitis (EAE). The EAE was treated with two catalytic inactive tPA variant proteins: S(481)A and S(481)A + KHRR(296-299)AAAA. EAE-induced tPA-/- mice presented

Patients with atopic asthma may become sensitised to the grain storage mite Dermatophagoides farinae (Der f), the house dust mite Dermatophagoides pteronyssinus (Der p) or both, but thus far little attention has been paid to date to possible variation in their pathophysiological effects. Here we present a side by side comparison of the effects of extracts of these two dust mites in a murine surrogate

Adoptive T cell transfer therapy (ACT) has emerged as a promising approach to cancer immunotherapy; however, the efficacy of ACT is limited by the T-cell suppressive activity of myeloid-derived suppressor cells (MDSCs), which accumulate in the tumor microenvironment after ACT. We sought to determine whether the efficacy of ACT could be enhanced by co-treatment with docetaxel, a taxane chemotherapy

BACKGROUND Piper nigrum L. (Piperaceae) is commonly used as a spice and traditional medicine in many countries. It has been reported to have anti-oxidant, anti-bacterial, anti-tumor, anti-mutagenic, anti-diabetic, and anti-inflammatory properties. However, the protective role of P. nigrum on epithelial function of upper respiratory tract injury in an allergic rhinitis (AR) mouse model has been unclear

The natural CD25+ FOXP3+ regulatory T cell (Treg) population is generated as a distinct lineage in the thymus, but the details of Treg development in humans remain unclear, and the timing of Treg commitment is also contested. Here we have analyzed the emergence of CD25+ cells at the CD4+CD8+ double positive (DP) stage in the human thymus. We show that these cells share T cell receptor repertoire with

B10 cells, a specific subset of regulatory B cells, are capable of regulating immune response and restricting inflammation and autoimmune disease progression by producing IL-10. B10 cells frequently change significantly during inflammation and autoimmunity. However, how B10 cell populations change in viral myocarditis (VMC) remains unclear. Therefore, this work was conducted to clarify the changes

Autologous C-kit+ cells robustly prolong cardiac allografts. As C-kit+ cells can transdifferentiate to hematopoietic cells as well as non-hematopoietic cells, we aimed to clarify the class(es) of C-kit-derived cell(s) required for cardiac allograft prolongation. Autologous C-kit+ cells were administered post-cardiac transplantation and allografts were evaluated for C-kit+ inoculum-derived cells. Results

Aging is characterized by significant immune remodeling at both cellular and molecular levels, also known as immunosenescence. Older adults often manifest a chronic low-grade inflammatory phenotype. These age-related immune system changes have increasingly been recognized not only to lead to immune functional decline and increased vulnerability to infections, but also to play an important role in many

Interleukin (IL)-35 strongly suppresses the immune effects of CD8+ T cells. However, the mechanisms mediating these effects are not clear. Here, we investigated the potential inhibitory mechanisms of IL-35 using proteomics technology. The changes of differentially expressed proteins (DEPs) were evaluated using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. IL-35

Here we used three different murine mammary carcinomas to study the immune environment associated with early tumor sites. While it was not surprising that the early immune response was predominated by macrophages and neutrophils, there were some novel findings at this early stage of disease. For instance, the macrophages and neutrophils expressed a mixed cytokine profile with TNF-α and TGF-β both produced

Disease recurrence after organ transplantation associated with graft failure is a major clinical challenge in autoimmune diseases. Primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune Hepatitis (AIH) are the three most common (autoimmune liver diseases) ALD for which liver transplantation (LT) is the most effective treatment option for patients with end-stage diseases

Immune cells including B and T lymphocytes have a remarkable ability to sense the physical perturbations through their surface expressed receptors. At the advent of modern imaging technologies paired with biophysical methods, we have gained the understanding of mechanical forces exerted by immune cells to perform their functions. This review will go over the imaging techniques already being used to

Intravital imaging of cutaneous immune responses has revealed intricate links between the skin’s structural properties, the immune cells that reside therein, and the carefully orchestrated migratory dynamics that enable rapid sensing and subsequent elimination of skin pathogens. In particular, the development of 2-photon intravital microscopy (2P-IVM), which enables the excitation of fluorescent molecules

Neutrophils are the first cellular responders of the immune system. They employ their impressive arsenal of microbicidal molecules to provide rapid and efficient defense against pathogens. However, the role of neutrophils extends far beyond microbial destruction to include tissue repair and remodeling, provision of signals to the adaptive immune system and body homeostasis. Intravital imaging has allowed

The lung represents a unique immune environment. The primary function of the lung is to enable gas exchange by facilitating the transfer of oxygen into and carbon dioxide out of the blood. However, as a direct byproduct of this process the lung is also constantly exposed to particles, allergens, and pathogens alongside air itself. Due to this, the pulmonary immune system exists in a fine balance between

The airway mucosa is the primary tissue site exposed to inhaled particulate matter, which includes pathogens and allergens. While most inhaled particles are eliminated from the airways via mucociliary clearance, some pathogens may penetrate the mucosal epithelial barrier and an effective activation of the mucosal immune system is required to prevent further pathogen spread. Similarly, inhaled environmental

Various immune cells are present in the skin and modulate the cutaneous immune response. In order to capture such dynamic phenomena, intravital imaging is an important technique and there is a possibility to provide substantial information that is not available using conventional histological analysis. Multiphoton microscope enable direct, three-dimensional, minimally invasive imaging of biological

High-mobility group box 1 (HMGB1) concentration in serum or plasma has been proposed as an important biological marker in various inflammation-related pathologies. We previously showed that low titer autoantibodies against HMGB1 could emerge during the course of sepsis. Importantly their presence was positively related with patients' survival. In this study, we focused on plasma samples from 2 patients

Quantitative gene expression profiling of cardiac allografts characterizes the phenotype of the alloimmune response, yields information regarding differential effects that may be associated with various anti-rejection drug regimens, and generates testable hypotheses regarding the pathogenesis of the chronic rejection lesions typically observed in non-human primate heart transplant models. The goal

The coinhibitory molecule B7-H4, an important member of the B7 family, is abnormally expressed in tumors, inflammation and autoimmune diseases. B7-H4 negatively regulates T cell immune response and promotes immune escape by inhibiting the proliferation, cytokine secretion, and cell cycle of T cells. Moreover, B7-H4 plays an extremely important role in tumorigenesis and tumor development including cell

Immunosenescence is defined as the progressive deterioration of the immune system with aging. Immunosenescence stifles the generation of protective B and T cell-mediated adaptive immunity in response to various pathogens, resulting in increased disease susceptibility and severity in the elderly population. In particular, immunosenescence has major impacts on the phenotype, function, and receptor repertoire