Notes

Polysaccharide consumption locus and also CAZYme genome repertoires expose diverse ecological variation regarding Prevotella species.
Several amino acids (AA) are known to regulate key metabolic pathways that are crucial for immune responses. In particular, arginine (ARG) appears to have important roles regarding immune modulation since it is required for macrophage responses and lymphocyte development. Moreover, citrulline (CIT) is a precursor of arginine, and it was reported as an alternative to ARG for improving macrophage function in mammals. The present study aimed to explore the effects of dietary ARG and CIT supplementation on the gilthead seabream (Sparus aurata) immune status. Triplicate groups of fish (23.1 ± 0.4 g) were either fed a control diet (CTRL) with a balanced AA profile, or the CTRL diet supplemented with graded levels of ARG or CIT (i.e., 0.5 and 1% of feed; ARG1, CIT1, ARG2, and CIT2, respectively). After 2 and 4 weeks of feeding, fish were euthanized and blood was collected for blood smears, plasma for humoral immune parameters and shotgun proteomics, and head-kidney tissue for the measurement of health-related transc increasing trend in a dose-dependent manner. The colony-stimulating factor 1 receptor tended to be up-regulated at the final sampling point regardless of dietary treatments. Data from this study point to an immunostimulatory effect of dietary ARG or CIT supplementation after 4 weeks of feeding in the gilthead seabream, particularly when supplemented at a 1% inclusion level.Hematopoietic stem cells (HSC) reside in the bone marrow (BM) within a specialized micro-environment, the HSC niche, which comprises several cellular constituents. These include cells of mesenchymal origin, endothelial cells and HSC progeny, such as megakaryocytes and macrophages. The BM niche and its cell populations ensure the functional preservation of HSCs. During infection or systemic inflammation, HSCs adapt to and respond directly to inflammatory stimuli, such as pathogen-derived signals and elicited cytokines, in a process termed emergency myelopoiesis, which includes HSC activation, expansion, and enhanced myeloid differentiation. The cell populations of the niche participate in the regulation of emergency myelopoiesis, in part through secretion of paracrine factors in response to pro-inflammatory stimuli, thereby indirectly affecting HSC function. Here, we review the crosstalk between HSCs and cell populations in the BM niche, specifically focusing on the adaptation of the HSC niche to inflammation and how this inflammatory adaptation may, in turn, regulate emergency myelopoiesis.Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common antibody-mediated encephalitis. There are several studies on B cell repertoire of anti-NMDAR encephalitis in Caucasians. Here, the cerebrospinal fluid (CSF) samples of 12 Chinese patients with first-episode anti-NMDAR encephalitis were collected to investigate the B cell receptor (BCR) binding to NMDAR by single cell amplification of BCR and Sanger sequencing. BCR data of healthy persons, and of patients with anti-leucine-rich glioma inactivated 1 (anti-LGI1) encephalitis, multiple sclerosis (MS), and neuromyelitis optica spectrum disorder (NMOSD) from the public databases were used as control. A heavy chain common clone IGHV1-18*04,IGHD1-26*01/ IGHD2-2*03/IGHD2-8*01, IGHJ3*02_(CDR3) ARVGSKYGFETFDI was found in 11 of 12 enrolled patients but not in the comparison data set. In addition, 4 shared clonotypes were found among these patients, and three of them contained the common clone. This study also revealed that the antibody gene family usage preference between patients and healthy controls were different, while they had similar antibody mutation rate. Our findings may have potential clinical implications for the diagnosis of anti-NMDAR encephalitis.Objectives The mechanism and immunoregulatory role of human natural killer (NK) cells in acute graft-vs.-host-disease (aGVHD) remains unclear. This study quantitatively analyzed the cytotoxicity of donor NK cells toward allo-reactive T cells, and investigated their relationship with acute GVHD (aGVHD). Methods We evaluated NK dose, subgroup, and receptor expression in allografts from 98 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). A CD107a degranulating assay was used as a quantitative detection method for the cytotoxic function of donor NK cells to allo-reactive T cells. In antibody-blocking assay, NK cells were pre-treated with anti-DNAM-1(CD226), anti-NKG2D, anti-NKP46, or anti-NKG-2A monoclonal antibodies (mAbs) before the degranulating assay. Results NK cells in allografts effectively inhibited auto-T cell proliferation following alloantigen stimulation, selectively killing alloantigen activated T cells. NKG2A- NK cell subgroups showed higher levels of CD107a degeveal that the degranulation activity of NK in allografts toward allo-activated T cells was associated with the occurrence and the severity of aGVHD, after allogeneic stem cell transplantation. This suggested that cytotoxicity of donor NK cells to allo-reactive T cells have important roles in aGVHD regulation.A large body of research implicates the brain and fat body (liver equivalent) as central players in coordinating growth and nutritional homeostasis in multicellular animals. In this regard, an underlying connection between immune cells and growth is also evident, although mechanistic understanding of this cross-talk is scarce. Here, we explore the importance of innate immune cells in animal growth during homeostasis and in conditions of nutrient stress. We report that Drosophila larvae lacking blood cells eclose as small adults and show signs of insulin insensitivity. Moreover, when exposed to dietary stress of a high-sucrose diet (HSD), these animals are further growth retarded than normally seen in regular animals raised on HSD. In contrast, larvae carrying increased number of activated macrophage-like plasmatocytes show no defects in adult growth when raised on HSD and grow to sizes almost comparable with that seen with regular diet. These observations imply a central role for immune cell activity in growth control. Mechanistically, our findings reveal a surprising influence of immune cells on balancing fat body inflammation and insulin signaling under conditions of homeostasis and nutrient overload as a means to coordinate systemic metabolism and adult growth. This work integrates both the cellular and humoral arm of the innate immune system in organismal growth homeostasis, the implications of which may be broadly conserved across mammalian systems as well.Colorectal cancer (CRC) remains one of the most common malignancies diagnosed worldwide. The pathogenesis of CRC is complex and involves, among others, accumulation of genetic predispositions and epigenetic factors, dietary habits, alterations in gut microbiota, and lack of physical activity. A growing body of evidence suggests that immune cells play different roles in CRC, comprising both pro- and anti-tumorigenic functions. Immunosuppression observed during cancer development and progression is a result of the orchestration of many cell types, including myeloid-derived suppressor cells (MDSCs). MDSCs, along with other cells, stimulate tumor growth, angiogenesis, and formation of metastases. This article focuses on MDSCs in relation to their role in the initiation and progression of CRC. Possible forms of immunotherapies targeting MDSCs in CRC are also discussed.Endotoxin tolerance represents a safeguard mechanism for preventing detrimental prolonged inflammation and exaggerated immune/inflammatory responses from innate immune cells to recurrent harmless pathogens. On the other hand, excessive immune tolerance can contribute to pathological immunosuppression, e.g., as present in sepsis. Monocyte activation is accompanied by intracellular metabolic rearrangements that are reportedly orchestrated by the metabolic signaling node mTORC1. mTORC1-dependent metabolic re-wiring plays a major role in monocyte/macrophage polarization, but whether mTORC1 participates in the induction of endotoxin tolerance and other immune adaptive programs, such as immune training, is not clear. This connection has been difficult to test in the past due to the lack of appropriate models of human endotoxin tolerance allowing for the genetic manipulation of mTORC1. Selleck Cytidine We have addressed this shortcoming by investigating monocytes from tuberous sclerosis (TSC) patients that feature a functional loss of the tumor suppressor TSC1/2 and a concomitant hyperactivation of mTORC1. Subjecting these cells to various protocols of immune priming and adaptation showed that the TSC monocytes are not compromised in the induction of tolerance. Analogously, we find that pharmacological mTORC1 inhibition does not prevent endotoxin tolerance induction in human monocytes. Interestingly, neither manipulation affected the capacity of activated monocytes to switch to increased lactic fermentation. In sum, our findings document that mTORC1 is unlikely to be involved in the induction of endotoxin tolerance in human monocytes and argue against a causal link between an mTORC1-dependent metabolic switch and the induction of immune tolerance.The aryl hydrocarbon receptor (AHR) is a ligand-activated transcriptional factor widely expressed in immune cells. Its ligands range from xenobiotics and natural substances to metabolites, which renders it capable of sensing and responding to a variety of environmental cues. Although AHR signaling has long been recognized to be implicated in the pathogenesis of autoimmune disorders, such as rheumatoid arthritis (RA), colitis, and systemic lupus erythematosus (SLE), its effect on the pathogenesis of type 1 diabetes (T1D) remains less understood. In this review, we intend to summarize its potential implication in T1D pathogenesis and to sort out the related regulatory mechanisms in different types of immune cells. Emerging evidence supports that β cell destruction caused by autoimmune responses can be rectified by AHR signaling. Upon activation by its ligands, AHR not only modulates the development and functionality of immune cells, but also suppresses the expression of inflammatory cytokines, through which AHR attenuates autoimmune responses during the course of T1D development. Since AHR-initiated biological effects vary between different types of ligands, additional studies would be necessary to characterize or de novo synthesize effective and safe ligands aimed to replenish our arsenal in fighting autoimmune responses and β mass loss in a T1D setting.Chronic graft-vs.-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have shown that autoantibodies play an important role in the development of cGVHD. Anti-nuclear autoantibodies (ANA) is the most frequently detected autoantibodies in patients with cGVHD, but the role of anti-Ro52 autoantibodies (anti-Ro52) in cGVHD remains largely unknown. In this study, we analyzed autoantibodies from 84 patients after allo-HSCT, including 42 with active cGVHD and 42 without cGVHD. Autoantibodies were found in 36 (42.9%) patients. Among these autoantibody-positive patients, 28 (77.8%) patients had active cGVHD. The most frequent autoantibodies in patients with active cGVHD were ANA (50.0%), anti-Ro52 (28.6%) and anti-mitochondrial autoantibodies type 2 (4.8%). We further explored the association between anti-Ro52 and cGVHD. Patients with active cGVHD had higher anti-Ro52 levels than patients without cGVHD (P less then 0.
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