STTT makes new progress!

iNature functional IL-10-secreting B cells are considered functional regulatory B (Breg) cells; however, direct evidence on the phenotype, regulation, and functional and clinical relevance of human IL-10-secreting Breg cells is still lacking
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On April 18, 2022, Chen Yun from Nanjing Medical University, Wang Xuehao and Kuang Dongming from Sun Yat-Sen University jointly published an online article entitled "c-Myc-driven glycolysis polarizes functional regulatory B cells that trigger pathogenic inflammatory inflammatory disease" in Signal Transduction and Targeted Therapy (IF=18).
Responses", which demonstrated that despite the anti-inflammatory effects of IL-10 itself, IL-10+ functional Breg cells from patients with systemic lupus erythematosus (SLE) displayed aggressive inflammatory features
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These features shift its function from inducing CD8+ T cell tolerance to inducing pathogenic CD4+ T cell responses
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Functional Breg cells polarized by environmental factors such as CPG-DNA or directly isolated from SLE patients mainly exhibit a CD24intCD27−CD38−CD69+/hi phenotype distinct from their precursors
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Mechanistically, MAPK/ERK/P38-triggered sequential oncogenic c-Myc upregulation and enhanced glycolysis are necessary for the generation and maintenance of functional Breg cells
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Consistently, strategies to eliminate ERK, p38, c-Myc and/or cellular glycolytic activity can effectively abolish the pathogenic effects triggered by functional Breg cells
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On March 9, 2022, the team of Chen Yun from Nanjing Medical University published a research paper titled "Gut microbiota-derived short-chain fatty acids regulates group 3 innate lymphoid cells in hepatocellular carcinoma" in Hepatology (IF=17).
Modification of bacteria, alteration of SCFAs, reduction of infiltration of IL17A-producing ILC3s, and combination with immune checkpoint inhibitors will contribute to the clinical treatment of HCC (click to read)
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On March 4, 2022, Chen Yun and Dai Juncheng of Nanjing Medical University jointly published a research paper entitled "Single-cell profiling of human CD127+ innate lymphoid cells reveals diverse immune phenotypes in hepatocellular carcinoma" in Hepatology (IF=17).
Single-cell RNA sequencing (scRNA-seq) analysis of sorted hepatic ILC cells from human HCC patients was performed and validated using flow cytometry, multiplex immunofluorescence staining, and functional experiments
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Furthermore, this study applied a selection strategy to enrich the ILC population in HCC samples to investigate the effect of B cells on the immune response of ICOS+ ILC2 cells
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Dysregulation of ILCs manifests as changes in cell numbers or subpopulation ratios in HCC
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Seven subsets of 3,433 ILCs were identified as having unique properties, with ICOS+ILC2a being preferentially enriched in HCC and associated with poor prognosis
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In conclusion, this study provides new insights into B cell-driven innate type 2 inflammation and a potential strategy for HCC immunotherapy (click to read)
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Regulatory B (Breg) cells are now considered suppressor cells that support immune tolerance
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A common feature of all described Breg subsets is their ability to release IL-10, and IL-10 release is widely used to define functional Breg cells
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However, in addition to producing IL-10, Breg cells express other molecules (eg, PD-L1, FasL, and granzyme B) that cause additional pathological effects
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Therefore, IL-10 is necessary, but not sufficient, for the activity of Breg cells
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Studies have established that in healthy individuals and patients, immature transitional CD24hiCD38hi B cells versus mature CD24hiCD27+ B cells represent important cellular sources of peripheral Breg cells
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Notably, the appearance of CD24hiCD38hi or CD24hiCD27+ phenotypes on B cells does not necessarily reflect their function
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Indeed, in patients with autoimmune diseases, CD24hiCD38hi and CD24hiCD27+ B cells hardly directly produce immunosuppressive functions
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Direct evidence supporting the role of functional Breg cells in the immunopathogenesis of human disease is still lacking
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Furthermore, a related question that must be addressed in this context is whether functional Breg cells exhibit unique functions that differ from known functions, and if so, how B cells exert these effects
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Metabolic reprogramming is emerging as a key process that reshapes immune cell differentiation and function
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Naive and memory B cells employ oxidative phosphorylation (OXPHOS) to provide basal energy requirements for metabolic quiescence
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In contrast, high-intensity glycolysis, together with aggressive OXPHOS, controls antibody secretion by effector B cells (also known as plasma cells), a process that relies on active glucose and amino acid uptake mechanisms
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Notably, although not directly related to B cells, glycolysis has also been identified as a potent activator of inflammatory responses, and OXPHOS has been implicated in anti-inflammatory responses and immune tolerance
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To date, the precise metabolic program of functional Breg cells that secrete IL-10 under pathological conditions is unknown
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In other words, assessing the metabolic program of functional Breg cells under pathological conditions is critical for understanding the polarization and functional status of these cells in immune pathogenesis
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Phenotypic characterization of IL-10-secreting Breg cells in SLE (Figure from Signal Transduction and Targeted Therapy) Systemic lupus erythematosus (SLE) is a potentially fatal autoimmune disease characterized by extensive inflammation and tissue damage , can affect any part of the body
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In SLE patients, deficits in suppressing cell function are necessary to enhance inflammation and the active stage of the disease
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It is postulated that Breg cells are a protective factor that hinders inflammatory responses based on their ability to produce IL-10
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However, by exploring the phenotypic characteristics and function of IL-10-secreting B cells in SLE patients, this study found that functional Breg cells act primarily as causative factors, but not as inflammation suppressors
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Functional Breg cells triggered by SLE pathological factors, such as CPG-DNA, exhibit a previously unrecognized CD24intCD27−CD38−CD69+/hi phenotype while producing numerous inflammatory mediators, a process triggered by MAPK/ERK/P38 signaling in a continuous manner Oncogenic c-Myc upregulation and enhanced glycolysis
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More importantly, this study demonstrates that these inflammatory signatures shift the functions of Breg cells from those that induce CD8+ T cell tolerance to those that induce inflammatory TH cell responses
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Thus, inhibiting the activity of ERK, P38, c-Myc, or the glycolytic enzyme PFKFB3 in functional Breg cells from patients with SLE could effectively attenuate the polarization of pathogenic inflammatory TH cell subsets
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