Mucosal-associated invariant T (MAIT) cells are innate-like T cells responsible for mucosal immunity in the respiratory and intestinal tracts. Here we present a flow-cytometry-based assay to measure the cytolytic activity of murine MAIT cells and natural killer (NK) cells. We describe steps for differentiating MAIT-like cells from the induced pluripotent stem cells prepared from MAIT cells (reMAIT cells), NK cell isolation, co-culture with target tumor cells, and staining to distinguish dead cells from live cells.
View Article and Find Full Text PDFThe function of mucosal-associated invariant T (MAIT) cells, a burgeoning member of innate-like T cells abundant in humans and implicated in many diseases, remains obscure. To explore this, mice with a rearranged T cell receptor (TCR) α or β locus, specific for MAIT cells, were generated via induced pluripotent stem cells derived from MAIT cells and were designated Vα19 and Vβ8 mice, respectively. Both groups of mice expressed large numbers of MAIT cells.
View Article and Find Full Text PDFDespite recent advances in asthma treatments, the search for novel therapies remains necessary because there are still patients with recurrent asthma exacerbations and poor responses to the existing treatments. Since group 2 innate lymphoid cells (ILC2) play a pivotal role in asthma by triggering and exacerbating type 2 inflammation, controlling ILC2s function is key to combating severe asthma. Mucosal-associated invariant T (MAIT) cells are innate-like T cells abundant in humans and are activated both in a T cell receptor-dependent and -independent manner.
View Article and Find Full Text PDFMucosal-associated invariant T (MAIT) cells, a burgeoning type of the innate-like T cells, play a crucial role in maintaining immune homeostasis, particularly in host defense. Although many studies have implied the use of MAIT cells in tumor immunity, whether MAIT cells are pro-tumor or anti-tumor has remained elusive, as in the case for other innate-like T cells that possess dichotomous roles in tumor immunity. Although this difficulty persists where endogenous MAIT cells are the target for therapeutic intervention, the advent of induced pluripotent stem-cell-derived MAIT cells (reMAIT cells) will make it possible to harness these cells for immune cell therapy.
View Article and Find Full Text PDFMucosal-associated invariant T (MAIT) cells, a blossoming member of the innate-like T cells, play a pivotal role in host defense through engaging the mucosal immunity. Although it has been suggested that MAIT cells are somehow implicated in the allergic airway inflammation mediated by group 2 innate lymphoid cells (ILC2s) such as asthma, the precise role(s) of MAIT cells in such inflammation has remained elusive. To explore the possible roles of MAIT cells in the inflammation, we examined whether MAIT cells suppressed the production of T helper (Th) 2 and inflammatory cytokines from ILC2s, and constrained the proliferation of ILC2s, both of which are prerequisite for airway inflammation.
View Article and Find Full Text PDFMucosal-associated invariant T (MAIT) cells belong to a family of innate-like T cells that bridge innate and adaptive immunities. Although MAIT cells have been implicated in tumor immunity, it currently remains unclear whether they function as tumor-promoting or inhibitory cells. Therefore, we herein used induced pluripotent stem cell (iPSC) technology to investigate this issue.
View Article and Find Full Text PDFReprogramming differentiated cells into induced pluripotent stem cells (iPSCs) consists in dedifferentiation of the cells into the pluripotent state, i.e., stem cells.
View Article and Find Full Text PDFGlucose 6-phosphate dehydrogenase (G6PDH) catalyzes the first reaction in the oxidative pentose phosphate pathway. In green plant chloroplasts, G6PDH is a unique redox-regulated enzyme, since it is inactivated under the reducing conditions. This regulation is accomplished using a redox-active cysteine pair, which is conserved in plant G6PDH.
View Article and Find Full Text PDFAlthough antibiotics to inhibit bacterial growth and small compounds to interfere with the productive life cycle of human immunodeficiency virus (HIV) have successfully been used to control HIV infection, the recent emergence of the drug-resistant bacteria and viruses poses a serious concern for worldwide public health. Despite intensive scrutiny in developing novel antibiotics and drugs to overcome these problems, there is a dilemma such that once novel antibiotics are launched in markets, sooner or later antibiotic-resistant strains emerge. Thus, it is imperative to develop novel methods to avoid this vicious circle.
View Article and Find Full Text PDFis capable of surviving in a wide variety of environments and is considered to be among the antimicrobial-resistant bacteria of greatest public health concern in hospital settings. To clarify the role of houseflies () in disseminating this bacterium, we collected 99 individuals from 15 locations (9 farms and 6 urban areas) in Thailand. was isolated from 39 % (39/99) of these houseflies, with the isolation rates being similar in farms and urban areas.
View Article and Find Full Text PDFInfant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4 T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is considered a major cause of immunodeficiency. Monocytes and macrophages are important cells of innate immunity and also are targets of HIV/SIV infection.
View Article and Find Full Text PDFMucosal-associated invariant T cells (MAITs) are innate-like T cells that play a pivotal role in the host defense against infectious diseases, and are also implicated in autoimmune diseases, metabolic diseases, and cancer. Recent studies have shown that induced pluripotent stem cells (iPSCs) derived from MAITs selectively redifferentiate into MAITs without altering their antigen specificity. Such a selective differentiation is a prerequisite for the use of MAITs in cell therapy and/or regenerative medicine.
View Article and Find Full Text PDFNowadays, antibiotic resistance is a serious global health concern, for it is observed every- where on the earth. While antibiotic is effective for controlling pathogens, an inappropriate use of the antibiotic leads to antibiotic resistance. Given that the ability to develop novel anti- biotics is quite limited, a new strategy must be developed to fight against it.
View Article and Find Full Text PDFBackground: Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination, gliosis and axonal loss in the Central Nervous System. Although the etiology of the disease has remained enigmatic, recent studies have suggested a role of the innate-like T cells, called Mucosal Associated Invariant T cells (MAITs) in the pathophysiology. In the present study, we have analyzed the relative frequency of MAITs and the expression of the cell surface antigens in MAITs to seek a possible link to the disease.
View Article and Find Full Text PDFMice have frequently been used to model human diseases involving immune dysregulation such as autoimmune and inflammatory diseases. These models help elucidate the mechanisms underlying the disease and in the development of novel therapies. However, if mice are deficient in certain cells and/or effectors associated with human diseases, how can their functions be investigated in this species? Mucosal-associated invariant T (MAIT) cells, a novel innate-like T cell family member, are a good example.
View Article and Find Full Text PDFBackground: Fibromyalgia (FM) is defined as a widely distributed pain. While many rheumatologists and pain physicians have considered it to be a pain disorder, psychiatry, psychology, and general medicine have deemed it to be a syndrome (FMS) or psychosomatic disorder. The lack of concrete structural and/or pathological evidence has made patients suffer prejudice that FMS is a medically unexplained symptom, implying inauthenticity.
View Article and Find Full Text PDFMucosal-associated invariant T (MAIT) cells play an important physiological role in host pathogen defense and may also be involved in inflammatory disorders and multiple sclerosis. The rarity and inefficient expansion of these cells have hampered detailed analysis and application. Here, we report an induced pluripotent stem cell (iPSC)-based reprogramming approach for the expansion of functional MAIT cells.
View Article and Find Full Text PDFAbstract Somatic cell nuclear transfer allows the generation of cloned embryonic stem cells (ESC) and cloned mice from natural killer T (NKT) cells, an innate-type invariant T cell. The progeny of these cloned mice harboring a rearranged T cell receptor α loci specific for NKT cells, Vα14-Jα18, possess an increased number of NKT cells in the primary as well as in the secondary lymphoid organs. NKT cells in these mice are able to produce interferon-γ (IFN-γ) and interleukin-4 (IL-4) when stimulated with dendritic cells (DC) pulsed with an NKT cell agonist, α-galactosylceramide (α-GalCer).
View Article and Find Full Text PDFObjective: The metabolic syndrome is an important social problem affecting many people in developed countries. Obesity is a leading cause of this syndrome, hence understanding molecular mechanisms underlying obesity is of prime importance for preventive medicine to develop novel methods to alleviate the corresponding social cost as well as for pharmaceutical companies to develop antimetabolic drugs.
Methods: Since adipocytes play an important role in obesity, we explored the signaling pathways leading to differentiation of adipocytes.
Leptin, the product of the ob gene, plays important roles in the regulation of food intake and body weight through its receptor in the hypothalamus. To identify novel transcripts induced by leptin, we performed cDNA subtraction based on selective suppression of the polymerase chain reaction by using mRNA prepared from the forebrain of leptin-injected ob/ob mice. One of the genes isolated was a mouse homolog of human negative regulatory element-binding protein (NREBP).
View Article and Find Full Text PDFObjectives: The aim of the study was to clarify the change in image quality upon X-ray dose reduction and to re-analyse the possibility of X-ray dose reduction in photostimulable phosphor luminescence (PSPL) X-ray imaging systems. In addition, the study attempted to verify the usefulness of multiobjective frequency processing (MFP) and flexible noise control (FNC) for X-ray dose reduction.
Methods: Three PSPL X-ray imaging systems were used in this study.