B. performed experiments on HBV-infected patients, analysed data, prepared the figures and edited the manuscript; C.B. and F.G. analysed the expression of genes involved in IL-2 sensing on KCs; A.C. and L.N. generated the lentiviral vectors encoding IL-2; G.G.-A. generated recombinant adeno-associated viruses; W.V.B. and D.D.P. generated rLCMV vectors; M.K., R.O. and L.G.G. provided funding, conceptual advice and edited the manuscript; M.I. designed and coordinated the study, provided funding, analysed the data, and wrote the paper.
Background-The atheromodulating activity of B cells during the development of atherosclerosis is well documented, but the mechanisms by which these cells are regulated have not been investigated. Methods and Results-Here, we analyzed the contribution of Qa-1-restricted CD8 + regulatory T cells to the control of the T follicular helper-germinal center B-cell axis during atherogenesis. Genetic disruption of CD8 + regulatory T cell function in atherosclerosis-prone apolipoprotein E knockout mice resulted in overactivation of this axis in secondary lymphoid organs, led to the increased development of tertiary lymphoid organs in the aorta, and enhanced disease development. In contrast, restoring control of the T follicular helper-germinal center B-cell axis by blocking the ICOS-ICOSL pathway reduced the development of atherosclerosis and the formation of tertiary lymphoid organs. Moreover, analyses of human atherosclerotic aneurysmal arteries by flow cytometry, gene expression analysis, and immunofluorescence confirmed the presence of T follicular helper cells within tertiary lymphoid organs.
Conclusions-This study is the first to demonstrate that the T follicular helper-germinal center B-cell axis is proatherogenicand that CD8 + regulatory T cells control the germinal center reaction in both secondary and tertiary lymphoid organs. Therefore, disrupting this axis represents an innovative therapeutic approach.
The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers.
Highlights d KCs are required for in vivo reinvigoration of intrahepatically primed T cells by IL-2 d KCs respond to IL-2 and cross-present hepatocellular Ags d Single-cell RNA-seq identifies two distinct populations of KCs d KC2s have enriched IL-2 sensing machinery and Ag presentation capacity
CD31 signaling promotes the switching of proinflammatory macrophages to the reparative phenotype and favors the healing of experimental dissected aortas. Treatment with a drug-suitable CD31 agonist may facilitate the clinical management of ADIM.
We found that PCSK9 was inconsistently associated with CV events in populations with type 2 diabetes. The association may depend on the level of CV risk and the background treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.