Interferon regulatory factor 4 (IRF4) and 8 are members of the interferon regulatory factor family of transcription factors and have been shown to be essential for the development and function of T ...cells, macrophages and dendritic cells. A series of recent studies have further demonstrated critical functions for IRF4 and 8 at several stages of B-cell development including pre-B-cell development, receptor editing, germinal center reaction and plasma cell generation. Collectively, these new studies provide molecular insights into the function of IRF4 and 8 and underscore a requirement for IRF4 and 8 throughout B-cell development. This review focuses on the recent advances on the roles of IRF4 and 8 in B-cell development.
•We summarized the research on ecosystem services (ESs) in protected areas (PAs) conducted worldwide over a 26-year period.•We developed a framework consisting of four stages to evaluate the progress ...of ES applications.•Information on how ESs translated into decision-making tools for PA management is lacking.•Case studies conducted in PAs have primarily examined cultural and provisioning ESs.•The lack of studies at large temporal and spatial scales has led to a research gap in the evaluation of the effects of ES applications.
Protected areas (PAs) are globally important environmental management tools against the effects of human activities, as they support the conservation of marine biodiversity, habitats, ecosystems and the processes within them, as well as resources in a broad sense. However, the application of Ecosystem Services (ESs) research in the environmental management of PAs has not been elucidated and it still has obvious shortcomings. Here, we present the first systematic review of studies that have assessed the application of ES research in PAs, evaluated the beneficial evidence of using ES for PA management, and identified research gaps to be addressed for future work. The majority of the 84 studies examined were conducted in Europe (44.44%) and Asia (30.77%), and they primarily examined cultural and provisioning ESs. Most case studies focused on methodological design and lacked an understanding of the spatial and temporal evolution patterns of ESs and of the interaction between ESs and management decisions in PAs. Future studies of PAs should (1) identify the main ESs provided, (2) improve ESs assessment methods and data acquisition capabilities, and (3) assess how pressures from outside the boundaries of PAs affect their ability to maintain biodiversity and ESs in the long term.
Myeloid sarcoma is a rare manifestation of acute myeloid leukemia (AML) and is associated with poor overall survival (OS). The optimal treatment remains unclear. The study retrospectively evaluated ...118 patients with myeloid sarcoma who were treated at the First Affiliated Hospital of Zhengzhou University from January 2010 to July 2021. All cases were diagnosed by tissue biopsy. 41 patients underwent genetic mutation analysis. The most frequent genetic mutations were KIT (16.6%), followed by TET2 (14.6%), and NRAS (14.6%). The median survival time of 118 patients was 4 months (range, 1-51 months), while the median survival time of 11 patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) was 19 months (range, 8-51 months). 4 (36.4%) of the 11 patients experienced relapse within 1 year after transplantation. 1 patient died from a severe infection. Of the 6 surviving patients, 5 patients have received maintenance treatment with decitabine after transplantation, and all remained in a state of recurrence-free survival. Patients with myeloid sarcoma have a very unfavorable outcome. Allo-HSCT is an effective treatment option. Recurrence remains the main cause of transplant failure. Maintenance treatment with decitabine after transplantation can prolong the recurrence-free survival time, although these results must be verified in a study with expanded sample size.
Interferon regulatory factor 4 (IRF4) and IRF8 are critical regulators of immune system development and function. In B lymphocytes, IRF4 and IRF8 have been shown to control important events during ...their development and maturation including pre-B cell differentiation, induction of B cell tolerance pathways, marginal zone B cell development, germinal center reaction and plasma cell differentiation. Mechanistically, IRF4 and IRF8 are found to function redundantly to control certain stages of B cell development, but in other stages, they function nonredundantly to play distinct roles in B cell biology. In line with their essential roles in B cell development, deregulated expressions of IRF4 and IRF8 have been associated to the pathogenesis of several B cell malignancies and diseases. Recent studies have elucidated diverse transcriptional networks regulated by IRF4 and IRF8 at distinct B cell developmental stages and related malignancies. In this review we will discuss the recent advances for the roles of IRF4 and IRF8 during B cell development and associated diseases.
Pre-B lymphocytes consist of 2 distinct cell populations: large pre-B and small pre-B. The large pre-B cells are newly generated pre-B cells that express pre–B-cell receptor (pre-BCR) on the surface ...and are highly proliferative; small pre-B cells are derived from large pre-B cells that have down-regulated pre-BCR and withdrawn from cell cycle. The molecular events that mediate the transition from cycling pre-B to small, resting pre-B have not been fully elucidated. Here, we show that interferon regulatory factors 4 and 8 (IRF4,8) suppress surrogate light chain expression and down-regulate pre-BCR in pre-B cells. Our studies further reveal that IRF4,8 induce the expression of Ikaros and Aiolos in pre-B cells, and reconstitution of expression of either one is sufficient to suppress surrogate light chain expression and down-regulate pre-BCR in pre-B cells lacking IRF4,8. Interestingly, our results also indicate that pre-B cells undergo growth inhibition and cell-cycle arrest in the presence of IRF4,8. Moreover, we provide evidence that Ikaros and Aiolos are indispensable for the down-regulation of pre-BCR and the cell-cycle withdrawal mediated by IRF4,8. Thus, IRF4,8 orchestrate the transition from large pre-B to small pre-B cells by inducing the expression of Ikaros and Aiolos.
1 In an attempt to design a conditioning strategy with very low toxicity but considerable myelosuppressive activity and potential immune-enhancing effects for patients with high-risk MDS and MDS/MPN, ...we combined DEC and IDA with busulfan, cyclophosphamide, and fludarabine for a modified myeloablative regimen in this prospective, multicenter cohort study (hereafter referred to as the “DEC/IDA study”). With a sample size of 120 patients, the study had a power of more than 80%, using a 5% level of significance to show significance determined by a binomial distribution calculation with the expected and threshold 2-year relapse rates (RRs) of 10% and 20%, respectively. Univariate analysis for OS and RFS of the DEC/IDA study was conducted Supplementary Table 2, http://links.lww.com/CM9/B938. The subgroup survival analysis in patients with MDS-EB or sAML was performed for patients in the DEC/IDA study and the historical control cohort.
A role for IRF8 in B cell anergy Pathak, Simanta; Ma, Shibin; Shukla, Vipul ...
The Journal of immunology (1950),
12/2013, Letnik:
191, Številka:
12
Journal Article
Recenzirano
Odprti dostop
B cell central tolerance is a process through which self-reactive B cells are removed from the B cell repertoire. Self-reactive B cells are generally removed by receptor editing in the bone marrow ...and by anergy induction in the periphery. IRF8 is a critical transcriptional regulator of immune system development and function. A recent study showed that marginal zone B cell and B1 B cell populations are dramatically increased in IRF8-deficient mice, indicating that there are B cell-developmental defects in the absence of IRF8. In this article, we report that mice deficient for IRF8 produced anti-dsDNA Abs. Using a hen egg lysozyme double-transgenic model, we further demonstrate that B cell anergy was breached in IRF8-deficient mice. Although anergic B cells in the IRF8-proficient background were blocked at the transitional stage of development, anergic B cells in the IRF8-deficient background were able to mature further, which allowed them to regain responses to Ag stimulation. Interestingly, our results show that IRF8-deficient B cells were more sensitive to Ag stimulation and were resistant to Ag-induced cell death. Moreover, our results show that IRF8 was expressed at a high level in the anergic B cells, and an elevated level of IRF8 promoted apoptosis in the transitional B cells. Thus, our findings reveal a previously unrecognized function of IRF8 in B cell anergy induction.
To compare the efficacy and safety of venetoclax (VEN) in combination with chemotherapy (chemo) versus chemo alone in the treatment of acute myeloid leukemia (AML).
To compare the efficacy and/or ...safety of VEN+chemo versus chemotherapy alone for AML, PubMed, Embase, Web of Science, and the Cochrane Library were used to searching up to June 2023. Comparisons included complete remission (CR), CR with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), overall response rate (ORR), and adverse events (AEs).
A total of 9 articles were included, including 3124 patients. The baseline characteristics between two patient groups were similar. The combined analysis showed that compared with the group receiving chemo alone, the VEN+chemo group exhibited higher rates of CR, CRi, MLFS and ORR. Additionally, the VEN+chemo group had longer event-free survival (EFS) and overall survival (OS) durations. The incidence rates of AEs and serious AEs (SAEs) were similar between the two groups, but the early 30-day mortality rate was lower in the VEN+chemo group than in the chemo alone group.
The VEN+chemo therapy demonstrates significant efficacy and safety profile in AML patients. However, more prospective studies are needed in the future to provide more accurate and robust evidence for treatment selection in patients.
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023439288, identifier CRD42023439288.
IFN-regulatory factor 5 (IRF-5), a member of the IRF family, is a transcription factor that has a key role in the induction of the antiviral and inflammatory response. When compared with C57BL/6 ...mice, Irf5⁻/⁻ mice show higher susceptibility to viral infection and decreased serum levels of type I IFN and the inflammatory cytokines IL-6 and TNF-α. Here, we demonstrate that IRF-5 is involved in B-cell maturation and the stimulation of Blimp-1 expression. The Irf5⁻/⁻ mice develop an age-related splenomegaly, associated with a dramatic accumulation of CD19⁺B220⁻ B cells and a disruption of normal splenic architecture. Splenic B cells from Irf5⁻/⁻ mice also exhibited a decreased level of plasma cells. The CD19⁺ Irf5⁻/⁻ B cells show a defect in Toll-like receptor (TLR) 7- and TLR9-induced IL-6 production, and the aged Irf5⁻/⁻ mice have decreased serum levels of natural antibodies; however, the antigen-specific IgG1 primary response was already dependent in IRF-5 in young mice, although the IgM response was not. Analysis of the profile of transcription factors associated with plasma cell differentiation shows down-regulation of Blimp-1 expression, a master regulator of plasma cell differentiation, which can be reconstituted with ectopic IRF-5. IRF-5 stimulates transcription of the Prdm1 gene encoding Blimp-1 and binds to the IRF site in the Prdm1 promoter. Collectively, these results reveal that the age-related splenomegaly in Irf5⁻/⁻ mice is associated with an accumulation of CD19⁺B220⁻ B cells with impaired functions and show the role of IRF-5 in the direct regulation of the plasma cell commitment factor Blimp-1 and in B-cell terminal differentiation.
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