Clinical and Experimental Immunology

Dysregulation of leukocyte trafficking, lipid metabolism, and other metabolic processes are the hallmarks that underpin and drive pathology in obesity. Current clinical management targets alternations in lifestyle choices (e.g. exercise, weight loss) to limit the impact of the disease. Crucially, re-gaining control over the pathogenic cellular and molecular processes may offer an alternative, complementary strategy for obese patients. Here we investigate the impact of the immunopeptide, PEPITEM, on pancreas homeostasis and leukocyte trafficking in mice on high-fed obesogenic diet (HFD)...

Ankylosing Spondylitis is the main entity of a family of inflammatory diseases affecting many musculoskeletal (sacroiliac joints, spine, peripheral joints) and extra-musculoskeletal sites, termed spondyloarthritis. While it is debated whether disease onset is primarily driven by autoimmune or autoinflammatory processes, what is certain is that both innate and adaptive immune responses orchestrate local and systemic inflammation, which leads to chronic pain and immobility. Immune checkpoint signals are one key player for keeping the immune system in check and in balance, but their role in disease pathogenesis is still rather elusive...

Adjuvants, as the name indicates, are adjoined material aimed to assist in functioning as when added to vaccines they are meant to boost the effect and strongly stimulate the immune system. The response of the immune system can be unpredictable, and the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was developed to address possible adverse reactions of an autoimmune and inflammatory type that may be caused by adjuvants. While ASIA, as a syndrome, was coined and defined in 2011; reports describing patients with vague and nonspecific clinical symptoms following vaccinations appeared much earlier...

Allergen immunotherapy (AIT) is currently the only form of treatment that modifies allergic asthma. Pharmacotherapy alone seeks to control the symptoms of allergic asthma, allergic rhinitis, and other atopic conditions. In contrast, AIT can induce long-term physiological modifications through the immune system. AIT enables individuals to live improved lives many years after treatment ends, where they are desensitized to the allergen(s) used or no longer have significant allergic reactions upon allergen provocation...

T cells play key protective but also pathogenic roles in COVID-19. We studied expression of long non-coding RNAs (lncRNAs) in COVID-19 T cell transcriptomes by integrating previously published single-cell RNA sequencing datasets. The long intergenic non-coding RNA MALAT1 was the most highly transcribed lncRNA in T cells, with Th1 cells demonstrating the lowest and CD8+ resident memory cells the highest MALAT1 expression, amongst CD4+ and CD8+ T cells populations, respectively. We then identified gene signatures that covaried with MALAT1 in single T cells...

Endometriosis is a common inflammatory disorder in women of reproductive age due to an abnormal endometrial immune environment and is associated with infertility. This study aimed to systematically understand the endometrial leukocyte types, inflammatory environment, and impaired receptivity at single-cell resolution. We profiled single-cell RNA transcriptomes of 138,057 endometrial cells from endometriosis patients (n=6) and control (n=7), respectively, using 10x Genomics platform. We found that one cluster of epithelial cells that expressed PAEP and CXCL14 was mostly from the control during the window of implantation (WOI)...

Natural killer (NK) cells possess the innate ability to eliminate cancerous cells effectively. Their crucial role in immunosurveillance has been widely recognised and exploited for therapeutic intervention. Despite the fast-acting nature of NK cells, NK adoptive cell transfer lacks favourable response in some patients. Patient NK cells often display diminished phenotype in preventing cancer progression resulting in poor prognosis. Tumour microenvironment play a significant role in causing the downfall of NK cells in patients...

Cell interactions represent an important mechanism involved in the pathogenesis of chronic inflammation. The key S100 proteins A8 and A9 have been studied in several models of chronic inflammatory diseases with highly heterogeneous conclusions. In this context, the aim of this study was to determine the role of cell interactions on S100 protein production and their effect on cytokine production during cell interactions, between immune and stromal cells from synovium or skin. Peripheral blood mononuclear cells (PBMC) were cultured alone or with synoviocytes or skin fibroblasts, with or without phytohemagglutinin, exogenous A8, A9, A8/A9 proteins or anti-A8/A9 antibody...

(IL)-17A, the effective factor of Th17 cells acts on important pathological role in the pathogenesis of psoriasis. Notch1/hairy and split 1 (Hes1) and PI3K/AKT signaling pathways are interpenetrated and involved in Th17 cell differentiation and IL-17A production. In this present study, we used imiquimod (IMQ)-induced mouse psoriatic skin inflammation to explore the possible mechanism of Notch1/Hes1-PTEN/AKT/IL-17A feedback loop in psoriasis by employing AKT inhibitor LY294002 as an intervention with the methods of flow cytometry analysis, reverse transcription-quantitative polymerase chain reaction, western blot, co-immunoprecipitation and immunofluorescence...

Chronic Granulomatous Disease (CGD) is a rare primary immune disorder caused by mutations in one of the five subunits of the NADPH oxidase complex expressed in phagocytes. Two-thirds of CGD cases are caused by mutations in CYBB that encodes NOX2 or gp91 phox. Some rare X91 +-CGD point mutations lead to a loss-of-function but with a normal expression of the mutated NOX2 protein. It is therefore necessary to ensure that this mutation is indeed responsible for the loss of activity in order to make a safe diagnosis for genetic counselling...

T cells are important in preventing severe disease from SARS-CoV-2, but scalable and field-adaptable alternatives to expert T cell assays are needed. The interferon-gamma release assay QuantiFERON platform was developed to detect T cell responses to SARS-CoV-2 from whole blood with relatively basic equipment and flexibility of processing timelines. 48 participants with different infection and vaccination backgrounds were recruited. Whole blood samples were analysed using the QuantiFERON SARS-CoV-2 assay in parallel with the well-established 'Protective Immunity from T Cells in Healthcare workers' (PITCH) ELISpot, which can evaluate spike-specific T cell responses...

Eosinophilic esophagitis is a T cell-driven allergic condition hallmarked by eosinophil infiltration of the esophagus. Eosinophils exposed to proliferating T cells release galectin-10 and have T cell suppressive function in vitro. The aims of this study were to evaluate if eosinophils co-localize with T cells and release galectin-10 in the esophagus of patients with eosinophilic esophagitis. Esophageal biopsies from 20 patients with eosinophilic esophagitis were stained for major basic protein, galectin-10, CD4, CD8, CD16, and CD81 and analyzed by immunofluorescence confocal microscopy before and after topical corticosteroid treatment...

The immune system plays a critical role in protecting the host against infection, but is subject to numerous levels of control that are necessary to prevent pathological, tissue damaging responses. Inappropriate inflammatory immune responses to self-antigens, innocuous commensal microorganisms or environmental antigens can lead to chronic, debilitating and degenerative diseases. Regulatory T cells have an essential, non-redundant and dominant function in preventing pathological immune responses, as shown by the development of systemic fatal autoimmunity in humans and animals with a genetic deficiency in regulatory T cells...

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To investigate the features of circulating B cells, their expressing receptors, serum levels of B-cell activation factor of the TNF family (BAFF), and a proliferation-inducing ligand (APRIL) in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Blood samples from 24 patients with active AAV (a-AAV), 13 with inactive AAV (i-AAV), and 19 healthy controls (HC) were included in this study. The proportion of B cells and their expressing BAFF receptor (BAFF-R), transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), and B-cell maturation antigen were analyzed via flow cytometry...

Since April 2022, over 1000 children across 35 countries have developed episodes of acute hepatitis of unknown origin. At King's College Hospital, a total of 65 children were referred with acute hepatitis of unknown aetiology, with 10 of these children presenting with acute liver dysfunction leading to acute liver failure. Multiple hypotheses have been proposed and continue to be investigated worldwide. In this review, we explore the current understanding of potential aetiologies for this outbreak. We further characterize the proposed immunological mechanisms of liver injury in these cases...

Salivary gland epithelial cells (SGECs) play an active role in primary Sjogren's syndrome (pSS) pathogenesis. Quantitative and qualitative abnormalities of saliva might expose SGECs to chronic hyperosmolarity. We aimed to decipher the links between hyperosmolar stimulation of SGECs and lymphocytic infiltration of the salivary glands (SG) observed in pSS. RNAseq was performed on NS-SV-AC cells stimulated with hyperosmolar media containingNaCl (100mM) or sucrose (200mM), or with iso-osmolar (Iso) medium. RNAseq was performed on primary cultured SGECs from pSS and controls, in presence or not of B cells...

Regulatory B (Breg) cells can dampen inflammation, autoreactivity and transplant rejection. We investigated the frequencies, phenotypes and function of Breg cells in granulomatosis with polyangiitis (GPA) to gain further knowledge to whether there are numerical alterations or limitations of their ability to regulate T-cell function. Frequencies and phenotypes of CD24 hiCD27 + and CD24 hiCD38 hi B-cells in the blood were determined with flow cytometry in 37 GPA patients (22 in remission and 15 with active disease) and 31 healthy controls (HC)...

Head and neck squamous cell carcinomas (HNSCCs) evade immune responses through multiple resistance mechanisms. Extracellular vesicles (EVs) released by the tumor and interacting with immune cells induce immune dysfunction and contribute to tumor progression. This study evaluates the clinical relevance and impact on anti-tumor immune responses of gene signatures expressed in HNSCC and associated with EV production/release. Expression levels of two recently described gene sets were determined in the Cancer Genome Atlas (TCGA) Head and Neck Cancer cohort (n=522) and validated in the GSE65858 dataset (n=250) as well as a recently published single cell RNA sequencing dataset (n=18)...

Relapsing polychondritis (RP) is a rare inflammatory disease with significant individual heterogeneity that involves systemic organs. The diagnosis of RP mainly depends on the clinical manifestations; currently, there are no molecular biomarkers routinely evaluated in clinical practice. Biomarkers have diagnostic or monitoring values and can predict response to treatment or the disease course. Over the years, many biomarkers have been proposed to facilitate diagnosis and prognosis. Unfortunately, ideal biomarkers to diagnose RP have not yet been discovered...