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The ability to characterize immune cells and explore the molecular interactions that govern their functions has never been greater, fueled in recent years by the revolutionary advance of single‐cell analysis platforms. However, precisely how immune cells respond to different stimuli and where differentiation processes and effector functions operate remain incompletely understood. Inferring cellular fate within single‐cell transcriptomic analyses is now omnipresent, despite the assumptions typically required in such analyses. Recently developed experimental models support dynamic analyses of the immune response, providing insights into the temporal changes that occur within cells and the tissues in which such transitions occur. Here we will review these approaches and discuss how these can be combined with single‐cell technologies to develop a deeper understanding of the immune responses that should support the development of better therapeutic options for patients. [ABSTRACT FROM AUTHOR]

The gastrointestinal tract is colonized by trillions of commensal microorganisms that collectively form the microbiome and make essential contributions to organism homeostasis. The intestinal immune system must tolerate these beneficial commensals, whilst preventing pathogenic organisms from systemic spread. Humoral immunity plays a key role in this process, with large quantities of immunoglobulin (Ig)A secreted into the lumen on a daily basis, regulating the microbiome and preventing bacteria from encroaching on the epithelium. However, there is an increasing appreciation of the role of IgG antibodies in intestinal immunity, including beneficial effects in neonatal immune development, pathogen and tumour resistance, but also of pathological effects in driving chronic inflammation in inflammatory bowel disease (IBD). These antibody isotypes differ in effector function, with IgG exhibiting more proinflammatory capabilities compared with IgA. Therefore, the process that leads to the generation of different antibody isotypes, class‐switch recombination (CSR), requires careful regulation and is orchestrated by the immunological cues generated by the prevalent local challenge. In general, an initiating signal such as CD40 ligation on B cells leads to the induction of activation‐induced cytidine deaminase (AID), but a second cytokine‐mediated signal determines which Ig heavy chain is expressed. Whilst the cytokines driving intestinal IgA responses are well‐studied, there is less clarity on how IgG responses are generated in the intestine, and how these cues might become dysfunctional in IBD. Here, we review the key mechanisms regulating class switching to IgA vs IgG in the intestine, processes that could be therapeutically manipulated in infection and IBD. [ABSTRACT FROM AUTHOR]

There is an increasing appreciation that many innate and adaptive immune cell subsets permanently reside within non‐lymphoid organs, playing a critical role in tissue homeostasis and defense. The best characterized are macrophages and tissue‐resident T lymphocytes that work in concert with organ structural cells to generate appropriate immune responses and are functionally shaped by organ‐specific environmental cues. The interaction of tissue epithelial, endothelial and stromal cells is also required to attract, differentiate, polarize and maintain organ immune cells in their tissue niche. All of these processes require dynamic regulation of cellular transcriptional programmes, with epigenetic mechanisms playing a critical role, including DNA methylation and post‐translational histone modifications. A failure to appropriately regulate immune cell transcription inevitably results in inadequate or inappropriate immune responses and organ pathology. Here, with a focus on the mammalian kidney, an organ which generates differing regional environmental cues (including hypersalinity and hypoxia) due to its physiological functions, we will review the basic concepts of tissue immunity, discuss the technologies available to profile epigenetic modifications in tissue immune cells, including those that enable single‐cell profiling, and consider how these mechanisms influence the development, phenotype, activation and function of different tissue immune cell subsets, as well as the immunological function of structural cells. [ABSTRACT FROM AUTHOR]

Neutrophils are traditionally considered short‐lived, circulating innate immune cells that are rapidly recruited to sites of inflammation in response to infectious and inflammatory stimuli. Neutrophils efficiently internalize, kill or entrap pathogens, but their effector molecules may cause collateral tissue damage. More recently, it has been appreciated that neutrophils can also influence adaptive immunity. Lymph nodes (LNs) are immune cell‐rich secondary lymphoid organs that provide an ideal platform for cellular interaction and the integration of immunological information collected from local tissues. A variety of peripheral stimuli promote neutrophil migration to draining LNs via blood or lymphatics, utilizing differing molecular cues depending on the site of entry. Within LNs, neutrophils interact with other innate and adaptive cells. Crosstalk with subcapsular sinus macrophages contributes to the control of pathogen spread beyond the LN. Neutrophils can influence antigen presentation indirectly by interacting with DCs or directly by expressing major histocompatibility complex (MHC) and costimulatory molecules for antigen presentation. Interactions between neutrophils and adaptive lymphocytes can alter B‐cell antibody responses. Studies have shown conflicting results on whether neutrophils exert stimulatory or inhibitory effects on other LN immune cells, with stimulus‐specific and temporal differences in the outcome of these interactions. Furthermore, neutrophils have also been shown to traffick to LNs in homeostasis, with a potential role in immune surveillance, antigen capture and in shaping early adaptive responses in LNs. Understanding the mechanisms underpinning the effects of neutrophils on LN immune cells and adaptive immunity could facilitate the development of neutrophil‐targeted therapies in inflammatory diseases. [ABSTRACT FROM AUTHOR]

There is uncertainty about the safety of kidney transplantation during the SARS‐CoV‐2 pandemic due to the risk of donor transmission, nosocomial infection and immunosuppression use. We describe organ donation and transplant practice in the UK and assess whether kidney transplantation conferred a substantial risk of harm. Data from the UK transplant registry were used to describe kidney donation and transplant activity in the UK, and a detailed analysis of short‐term, single‐center, patient results in two periods: during the pre‐pandemic era from 30th December 2019 to 8th March 2020 ("Pre‐COVID era") and the 9th March 2020 to 19th May 2020 ("COVID era"). Donor and recipient numbers fell by more than half in the COVID compared to the pre‐COVID era in the UK, but there were more kidney transplants performed in our center (42 vs. 29 COVID vs. pre‐COVID respectively). Overall outcomes, including re‐operation, delayed graft function, primary non‐function, acute rejection, length of stay and graft survival were similar between COVID and pre‐COVID era. 6/71 patients became infected with SARS‐CoV‐2 but all were discharged without critical care requirement. Transplant outcomes have remained similar within the COVID period and no serious sequelae of SARS‐CoV‐2 infection were observed in the peri‐transplant period. [ABSTRACT FROM AUTHOR]

Antibody‐mediated rejection (ABMR) represents a major cause of late allograft loss in solid organ transplantation worldwide. This process is driven by donor‐specific antibodies (DSA), which develop either de‐novo or, in sensitized patients, are preformed at the time of transplantation. Effective targeting of ABMR has been hampered by a lack of robust randomized controlled trials (RCT), required for the regulatory approval of new therapeutics. In this review, we discuss the evidence behind the present "standard" of care and recent progress in the development of novel strategies targeting different aspects of the alloimmune humoral response, including naïve and memory B‐cell activation, the germinal centre reaction, plasma cell survival and antibody effector functions. In particular, we focus on co‐stimulation blockade and its combination with next‐generation proteasome inhibitors, new depleting monoclonal antibodies (anti‐CD19, anti‐BCMA, anti‐CD38, anti‐CD138), interleukin‐6 blockade, complement inhibition and DSA degradation. These treatment modalities, when used in the appropriate clinical context and combination, have the potential to finally improve long‐term allograft survival. [ABSTRACT FROM AUTHOR]

Cells represent the basic building blocks of living organisms. Accurate characterisation of cellular phenotype, intercellular signalling networks, and the spatial organisation of cells within organs is crucial to deliver a better understanding of the processes underpinning physiology, and the perturbations that lead to disease. Single-cell methodologies have increased rapidly in scale and scope in recent years and are set to generate important insights into human disease. Here, we review current practices in nephropathology, which are dominated by relatively simplemorphological descriptions of tissue biopsies based on their appearance using light microscopy. Bulk transcriptomics have more recently been used to explore glomerular and tubulointerstitial kidney disease, renal cancer, and the responses to injury and alloimmunity in kidney transplantation, generating novel disease insights and prognostic biomarkers. These studies set the stage for single-cell transcriptomic approaches that reveal cell-type-specific gene expression patterns in health and disease. These technologies allow genome-wide disease susceptibility genes to be interpreted with the knowledge of the specific cell populations within organs that express them, identifying candidate cell types for further study. Single-cell technologies are also moving beyond assaying individual cellular transcriptomes, to measuring the epigenetic landscape of single cells. Single-cell antigen-receptor gene sequencing also enables specific T- and B-cell clones to be tracked in different tissues and disease states. In the coming years these rich 'multi-omic' descriptions of kidney disease will enable histopathological descriptions to be comprehensively integrated with molecular phenotypes, enabling better disease classification and prognostication and the application of personalised treatment strategies. [ABSTRACT FROM AUTHOR]

Autoimmune diseases are characterized by adaptive immune responses against self-antigens, including humoral responses resulting in the production of autoantibodies. Autoantibodies generate inflammation by activating complement and engaging Fcγ receptors (FcγRs). The inhibitory receptor Fcγ RIIB plays a central role in regulating the generation of autoantibodies and their effector functions, which include activation of innate immune cells and the cellular arm of the adaptive immune system, via effects on antigen presentation to CD4 T cells. Polymorphisms in Fcγ RIIB have been associated with susceptibility to autoimmunity but protection against infections in humans and mice. In the last few years, new mechanisms by which Fcγ RIIB controls the adaptive immune response have been described. Notably, Fcγ RIIB has been shown to regulate germinal center B cells and dendritic cell migration, with potential impact on the development of autoimmune diseases. Recent work has also highlighted the implication of Fcγ RIIB on the regulation of the innate immune system, via inhibition of Toll-like receptor- and complement receptor-mediated activation. This review will provide an update on the role of Fcγ RIIB in adaptive immune responses in autoimmunity, and then focus on their emerging function in innate immunity. [ABSTRACT FROM AUTHOR]

The autoimmune disease systemic lupus erythematosus (SLE) is characterized by the deposition of immune complexes in organs such as the kidney. This occurs as a result of multiple immunological abnormalities, including the production of high levels of autoantibody and dysregulated handling of immune complexes. Receptors for the Fc portion of IgG are critically involved in immune complex handling and clearance and in the regulation of B-cell activation. Polymorphisms in the low-affinity Fcγ receptors have been associated with susceptibility to a number of autoimmune diseases, including SLE. We review the role of two such receptors in the pathogenesis of lupus—the inhibitory receptor FcγRIIB and the glycosylphosphatidylinositol-linked activatory receptor FcγRIIIB. Recent work has enhanced our understanding of the mechanism of action of the FcγRIIB I232T polymorphism and the overall role of this receptor in SLE. The human neutrophil antigen-1 allotypes of FcγRIIIB and the role of the receptor in SLE are discussed with regard to the recent determination of copy number variation in FCGR3B and the association of low copy number with SLE. [ABSTRACT FROM AUTHOR]

The article discusses the expression of neuronal genes in splenic B cells. This study is another evidence on biological similarities between the nervous system and the immune systems. It provides further explanation to the anti-inflammatory effects of acupuncture and the effects of nicotine to the immune system.