Microbiology & Immunology - Research Publications
Permanent URI for this collection
Search Results
1 - 4 of 4
-
ItemThe effects of B-cell-activating factor on the population size, maturation and function of murine natural killer cells(WILEY, 2022-11)The role of B-cell-activating factor (BAFF) in B-lymphocyte biology has been comprehensively studied, but its contributions to innate immunity remain unclear. Natural killer (NK) cells form the first line of defense against viruses and tumors, and have been shown to be defective in patients with systemic lupus erythematosus (SLE). The link between BAFF and NK cells in the development and progression of SLE remains unstudied. By assessing NK cell numbers in wild-type (WT), BAFF-/- (BAFF deficient), BAFF-R-/- (BAFF receptor deficient), TACI-/- (transmembrane activator and calcium modulator and cyclophilin ligand interactor deficient), BCMA-/- (B-cell maturation antigen deficient) and BAFF transgenic (Tg) mice, we observed that BAFF signaling through BAFF-R was essential for sustaining NK cell numbers in the spleen. However, according to the cell surface expression of CD27 and CD11b on NK cells, we found that BAFF was dispensable for NK cell maturation. Ex vivo and in vivo models showed that NK cells from BAFF-/- and BAFF Tg mice produced interferon-γ and killed tumor cells at a level similar to that in WT mice. Finally, we established that NK cells do not express receptors that interact with BAFF in the steady state or in the BAFF Tg mouse model of SLE. Our findings demonstrate that BAFF has an indirect effect on NK cell homeostasis and no effect on NK cell function.
-
ItemMolecular control of B-cell homeostasis in health and malignancy(WILEY, 2018-05)Altered B-cell homeostasis underlies a wide range of pathologies, from cancers to autoimmunity and immunodeficiency. The molecular safeguards against those disorders, which also allow effective immune responses, are therefore particularly critical. Here, we review recent findings detailing the fine control of B-cell homeostasis, during B-cell development, maturation in the periphery and during activation and differentiation into antibody-producing cells.
-
ItemNo Preview AvailableThe BAFF/APRIL system: Emerging functions beyond B cell biology and autoimmunity(ELSEVIER SCI LTD, 2013-06)The BAFF system plays a key role in the development of autoimmunity, especially in systemic lupus erythematosus (SLE). This often leads to the assumption that BAFF is mostly a B cell factor with a specific role in autoimmunity. Focus on BAFF and autoimmunity, driven by pharmaceutical successes with the recent approval of a novel targeted therapy Belimumab, has relegated other potential roles of BAFF to the background. Far from being SLE-specific, the BAFF system has a much broader relevance in infection, cancer and allergy. In this review, we provide the latest views on additional roles of the BAFF system in health and diseases, as well as an update on BAFF and autoimmunity, with particular focus on current clinical trials.
-
ItemMachine learning applied to whole-blood RNA-sequencing data uncovers distinct subsets of patients with systemic lupus erythematosus(WILEY, 2019)OBJECTIVES: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease that is difficult to treat. There is currently no optimal stratification of patients with SLE, and thus, responses to available treatments are unpredictable. Here, we developed a new stratification scheme for patients with SLE, based on the computational analysis of patients' whole-blood transcriptomes. METHODS: We applied machine learning approaches to RNA-sequencing (RNA-seq) data sets to stratify patients with SLE into four distinct clusters based on their gene expression profiles. A meta-analysis on three recently published whole-blood RNA-seq data sets was carried out, and an additional similar data set of 30 patients with SLE and 29 healthy donors was incorporated in this study; a total of 161 patients with SLE and 57 healthy donors were analysed. RESULTS: Examination of SLE clusters, as opposed to unstratified SLE patients, revealed underappreciated differences in the pattern of expression of disease-related genes relative to clinical presentation. Moreover, gene signatures correlated with flare activity were successfully identified. CONCLUSION: Given that SLE disease heterogeneity is a key challenge hindering the design of optimal clinical trials and the adequate management of patients, our approach opens a new possible avenue addressing this limitation via a greater understanding of SLE heterogeneity in humans. Stratification of patients based on gene expression signatures may be a valuable strategy allowing the identification of separate molecular mechanisms underpinning disease in SLE. Further, this approach may have a use in understanding the variability in responsiveness to therapeutics, thereby improving the design of clinical trials and advancing personalised therapy.