Huaxi Xu

Bio: Huaxi Xu is an academic researcher from Jiangsu University. The author has contributed to research in topics: Myeloid-derived Suppressor Cell & Arthritis. The author has an hindex of 38, co-authored 216 publications receiving 4926 citations. Previous affiliations of Huaxi Xu include Peking Union Medical College.

Increased frequency of circulating follicular helper T cells in patients with rheumatoid arthritis.

Abstract: Follicular helper T (Tfh) cells are recognized as a distinct CD4(+) helper T-cell subset, which provides for B-cell activation and production of specific antibody responses, and play a critical role in the development of autoimmune disease. So far, only one study investigated the circulating Tfh cells increased in a subset of SLE patients. Since relatively little is known about the Tfh cells in rheumatoid arthritis (RA) patients, in this study, Tfh-cell frequency, related cytokine IL-21, and transcription factor Bcl-6 were investigated in 53 patients with RA and 31 health controls. Firstly, we found that the frequency of CD4(+)CXCR5(+)ICOS(high) Tfh cells was increased significantly in the peripheral blood of RA patients, compared with that in healthy controls. It is known that Tfh cells are critical for directing the development of an antibody response by germinal centers B cells; secondly, we observed that the Tfh-cell frequency is accompanied by the level of anti-CCP antibody in RA patients. Furthermore, expression of Bcl-6 mRNA and plasma IL-21 concentrations in RA patients was increased. Taken together, these findings have shown that the increased frequency of circulating Tfh cells is correlated with elevated levels of anti-CCP antibody, indicating the possible involvement of Tfh cells in the disease progression of RA.

Cutting Edge: Novel Function of B Cell-Activating Factor in the Induction of IL-10–Producing Regulatory B Cells

Abstract: Although B cells have been shown to possess a regulatory function, microenvironmental factors or cytokines involved in the induction of regulatory B cells remain largely uncharacterized. B cell-activating factor (BAFF), a member of TNF family cytokines, is a key regulator for B cell maturation and function. In this study, we detected significantly increased numbers of IL-10–producing B cells in BAFF-treated B cell cultures, an effect specifically abrogated by neutralization of BAFF with TACI-Fc. BAFF-induced IL-10–producing B cells showed a distinct CD1d hi CD5 + phenotype, which were mainly derived from marginal zone B cells. Moreover, BAFF activated transcription factor AP-1 for binding to IL-10 promoter. Notably, BAFF treatment in vivo increased the number of IL-10–producing B cells in marginal zone regions. Furthermore, BAFF-induced IL-10–producing B cells possess a regulatory function both in vitro and in vivo. Taken together, our findings identify a novel function of BAFF in the induction of IL-10–producing regulatory B cells.

The Th17/Treg imbalance and cytokine environment in peripheral blood of patients with rheumatoid arthritis

Abstract: Broken Th17/Treg balance has been reported contributing to several inflammatory autoimmune diseases. The objective of the study was to investigate whether the Th17/Treg balance was impaired in the peripheral blood of patients with rheumatoid arthritis (RA). The frequencies of Treg cells and Th17 cells and mRNA expression of transcription factor RORγt and FoxP3 in peripheral blood of RA patients (n = 37) and healthy controls (n = 30) were determined by flow cytometry and real-time PCR, respectively. Eleven serum cytokines were analyzed by using cytometeric bead array (CBA). The results demonstrated that active RA patients exhibited increased peripheral Th17 cells, Th1- and Th17-related cytokines and RORγt expression while decreased Treg cells and FoxP3 expression. In addition, Th17/Treg ratios were positively correlated with serum concentrations of Th1- and Th17-related cytokines. In conclusion, our results indicated that Th17/Treg balance was broken in peripheral blood, which may play an important role in the development of RA.

Increased Frequency of Follicular Helper T Cells in Patients with Autoimmune Thyroid Disease

Abstract: Context: Follicular helper T (Tfh) cells exert an important role in the autoimmune diseases. Aim: Our study aimed to explore the role of Tfh cells in patients with autoimmune thyroid disease (AITD). Design: Tfh cell is a new subset regulating the antibody production of B cell. Previous studies implicated CD4+CXCR5+ICOShigh or CD4+CXCR5+PD-1high as the markers of circulating Tfh cells. Sixty-five patients with AITD and 30 healthy controls were enrolled in the current study. The percentages of circulating Tfh cells were assessed by flow cytometry. The correlation between the percentages of CD4+CXCR5+ICOShigh T cells and the levels of autoantibodies or hormones was also analyzed. Additionally, polyphasic methods were applied to investigate the status of Tfh cells in thyroid glands of Hashimoto's thyroiditis patients. Results: Increased percentages of circulating Tfh cells in AITD patients were detected, and a positive correlation between the percentages of circulating Tfh cells and the serum concentrations o...

β‐Glucan enhances antitumor immune responses by regulating differentiation and function of monocytic myeloid‐derived suppressor cells

Abstract: Myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and play a major role in tumor-induced immunosuppression, which hampers effective immuno-therapeutic approaches. β-Glucans have been reported to function as potent immuno-modulators to stimulate innate and adaptive immune responses, which contributes to their antitumor property. Here, we investigated the effect of particulate β-glucans on MDSCs and found that β-glucan treatment could promote the differentiation of M-MDSCs (monocytic MDSCs) into a more mature CD11c(+) F4/80(+) Ly6C(low) population via dectin-1 pathway in vitro, which is NF-κB dependent, and the suppressive function of M-MDSCs was significantly decreased. Treatment of orally administered yeast-derived particulate β-glucan drastically downregulated MDSCs but increased the infiltrated DCs and macrophages in tumor-bearing mice, thus eliciting CTL and Th1 responses, inhibiting the suppressive activity of regulatory T cells, thereby leading to the delayed tumor progression. We show here for the first time that β-glucans induce the differentiation of MDSCs and inhibit the regulatory function of MDSCs, therefore revealing a novel mechanism for β-glucans in immunotherapy and suggesting their potential clinical benefit.

“Bioinformatics” 특집을 내면서

Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota

Abstract: Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis–specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade.

Partitioning heritability by functional annotation using genome-wide association summary statistics.

Abstract: Recent work has demonstrated that some functional categories of the genome contribute disproportionately to the heritability of complex diseases. Here we analyze a broad set of functional elements, including cell type-specific elements, to estimate their polygenic contributions to heritability in genome-wide association studies (GWAS) of 17 complex diseases and traits with an average sample size of 73,599. To enable this analysis, we introduce a new method, stratified LD score regression, for partitioning heritability from GWAS summary statistics while accounting for linked markers. This new method is computationally tractable at very large sample sizes and leverages genome-wide information. Our findings include a large enrichment of heritability in conserved regions across many traits, a very large immunological disease-specific enrichment of heritability in FANTOM5 enhancers and many cell type-specific enrichments, including significant enrichment of central nervous system cell types in the heritability of body mass index, age at menarche, educational attainment and smoking behavior.

The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients

Abstract: Anti–PD-1–based immunotherapy has had a major impact on cancer treatment but has only benefited a subset of patients. Among the variables that could contribute to interpatient heterogeneity is differential composition of the patients’ microbiome, which has been shown to affect antitumor immunity and immunotherapy efficacy in preclinical mouse models. We analyzed baseline stool samples from metastatic melanoma patients before immunotherapy treatment, through an integration of 16 S ribosomal RNA gene sequencing, metagenomic shotgun sequencing, and quantitative polymerase chain reaction for selected bacteria. A significant association was observed between commensal microbial composition and clinical response. Bacterial species more abundant in responders included Bifidobacterium longum , Collinsella aerofaciens , and Enterococcus faecium. Reconstitution of germ-free mice with fecal material from responding patients could lead to improved tumor control, augmented T cell responses, and greater efficacy of anti–PD-L1 therapy. Our results suggest that the commensal microbiome may have a mechanistic impact on antitumor immunity in human cancer patients.

Approaches to treat immune hot, altered and cold tumours with combination immunotherapies

Abstract: Immunotherapies are the most rapidly growing drug class and have a major impact in oncology and on human health. It is increasingly clear that the effectiveness of immunomodulatory strategies depends on the presence of a baseline immune response and on unleashing of pre-existing immunity. Therefore, a general consensus emerged on the central part played by effector T cells in the antitumour responses. Recent technological, analytical and mechanistic advances in immunology have enabled the identification of patients who are more likely to respond to immunotherapy. In this Review, we focus on defining hot, altered and cold tumours, the complexity of the tumour microenvironment, the Immunoscore and immune contexture of tumours, and we describe approaches to treat such tumours with combination immunotherapies, including checkpoint inhibitors. In the upcoming era of combination immunotherapy, it is becoming critical to understand the mechanisms responsible for hot, altered or cold immune tumours in order to boost a weak antitumour immunity. The impact of combination therapy on the immune response to convert an immune cold into a hot tumour will be discussed.