Myeloid and Mast Cell Progenitors Are Elevated in Atopic Dermatitis.

Chronic spontaneous urticaria and atopic dermatitis (AD) are chronic skin disorders characterized by itch. Although mast cells play an integral role in the pathogenesis of chronic spontaneous urticaria, their role in AD is unclear, having a contributory role in a disease largely driven by T helper 2 polarization. Despite this, the role of mast cells in AD is important, given their release of proinflammatory mediators.

Acellular Pertussis Vaccines Induce CD8 and CD4 Regulatory T Cells That Suppress Protective Tissue-Resident Memory CD4 T Cells, in Part via IL-10.

Tissue-resident memory T (T) cells play a key role in sustained protective immunity against Bordetella pertussis infection of the nasal mucosa. Current alum-adjuvanted acellular pertussis (aP) vaccines protect against severe pertussis disease but fail to prevent nasal infection with B. pertussis.

Towards Personalised Therapy in Chronic Spontaneous Urticaria: Advancing From Endotype to Clinical Response.

Chronic spontaneous urticaria (CSU) is a skin disorder characterised by recurrent hives and swellings that has a profound effect upon quality of life. Current guidelines for the management of CSU outline sequential use of standard dosing nonsedating H1 antihistamines, fourfold dose antihistamines and the anti-IgE monoclonal antibody omalizumab. A proportion of patients will have partial response or no response to omalizumab despite uptitration of dose.

Neonatal infection with promotes autism-like phenotypes in mice.

Autism spectrum disorder (ASD) has been linked with infections early in life. Here we demonstrate that the infection of neonatal mice with the respiratory pathogen leads to neuroinflammation, neurodevelopmental defects, and ASD-like behaviors. Following the respiratory challenge of neonatal mice with multiple atypical CNS findings were observed including blood-brain barrier disruption, dissemination of live bacteria to the brain with the concomitant infiltration of inflammatory monocytes, neutrophils, and activated IL-17A- and IFN-γ-producing CD4 T cells.

Loss of synovial tissue macrophage homeostasis precedes rheumatoid arthritis clinical onset.

This study performed an in-depth investigation into the myeloid cellular landscape in the synovium of patients with rheumatoid arthritis (RA), "individuals at risk" of RA, and healthy controls (HC). Flow cytometric analysis demonstrated the presence of a CD40-expressing CD206CD163 macrophage population dominating the inflamed RA synovium, associated with disease activity and treatment response. In-depth RNA sequencing and metabolic analysis demonstrated that this macrophage population is transcriptionally distinct, displaying unique inflammatory and tissue-resident gene signatures, has a stable bioenergetic profile, and regulates stromal cell responses.

PD-1 regulation of pathogenic IL-17-secreting γδ T cells in experimental autoimmune encephalomyelitis.

The PD-1-PD-L1 immune checkpoint helps to maintain self-tolerance and prevent the development of autoimmune diseases. Immune checkpoint inhibitors are successful immunotherapeutics for several cancers, but responding patients can develop immune-mediated adverse events. It is well established that PD-1 regulates CD4 and CD8 T-cell responses, but its role in controlling the activation of pathogenic γδ T cells is less clear.

LinCD117CD34FcεRI progenitor cells are increased in chronic spontaneous urticaria and predict clinical responsiveness to anti-IgE therapy.

Background: Chronic spontaneous urticaria (CSU) is a common, debilitating skin disorder characterized by recurring episodes of raised, itchy and sometimes painful wheals lasting longer than 6 weeks. CSU is mediated by mast cells which are absent from peripheral blood. However, lineageCD34CD117FcεRI cells in blood have previously been shown to represent a mast cell precursor.

Management of comorbidities in difficult and severe asthma.

Difficult-to-treat and severe asthma are challenging clinical entities. In the face of suboptimal asthma control, the temptation for clinicians is to reflexively escalate asthma-directed therapy, including increasing exposure to corticosteroids and commencement of costly but potent biologic therapies. However, asthma control is objectively and subjectively assessed based on measurable parameters (such as exacerbations or variability in pulmonary physiology), symptoms and patient histories.

Inflammation in the pathogenesis of depression: a disorder of neuroimmune origin.

There are several hypotheses concerning the underlying pathophysiological mechanisms of major depression, which centre largely around adaptive changes in neuronal transmission and plasticity, neurogenesis, and circuit and regional connectivity. The immune and endocrine systems are commonly implicated in driving these changes. An intricate interaction of stress hormones, innate immune cells and the actions of soluble mediators of immunity within the nervous system is described as being associated with the symptoms of depression.

Targeting the NLRP3 inflammasome reduces inflammation in hidradenitis suppurativa skin.

Background: Treatment for the debilitating disease hidradenitis suppurativa (HS) is inadequate in many patients. Despite an incidence of approximately 1%, HS is often under-recognized and underdiagnosed, and is associated with a high morbidity and poor quality of life.

Objectives: To gain a better understanding of the pathogenesis of HS, in order to design new therapeutic strategies.

Innate lymphoid cell (ILC) subsets are enriched in the skin of patients with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease manifested as painful inflamed lesions including deep-seated nodules, abscesses and sinus tracts. The exact aetiology of HS is unclear. Recent evidence suggests that immune dysregulation plays a crucial role in pathogenesis and disease progression.

IL-17 mediates protective immunity against nasal infection with Bordetella pertussis by mobilizing neutrophils, especially Siglec-F neutrophils.

Understanding the mechanism of protective immunity in the nasal mucosae is central to the design of more effective vaccines that prevent nasal infection and transmission of Bordetella pertussis. We found significant infiltration of IL-17-secreting CD4 tissue-resident memory T (T) cells and Siglec-F neutrophils into the nasal tissue during primary infection with B. pertussis.

Optimisation and comparison of orthogonal methods for separation and characterisation of extracellular vesicles to investigate how representative infant milk formula is of milk.

Many infants are fed infant milk formula (IMF). However, IMF production from skim milk (SM) involves harsh treatment. So, we hypothesised that the quantity and/or quality of extracellular vesicles (EVs) in IMF may be reduced.

Extracellular vesicles report on the MET status of their cells of origin regardless of the method used for their isolation.

MET pathway is an important actionable target across many solid tumour types and several MET inhibitors have been developed. Extracellular vesicles (EVs) are proposed to be mini-maps of their cells of origin. However, the potential of EVs to report on the MET status of their cells of origin is unknown.

Pathogenic, glycolytic PD-1+ B cells accumulate in the hypoxic RA joint.

While autoantibodies are used in the diagnosis of rheumatoid arthritis (RA), the function of B cells in the inflamed joint remains elusive. Extensive flow cytometric characterization and SPICE algorithm analyses of single-cell synovial tissue from patients with RA revealed the accumulation of switched and double-negative memory programmed death-1 receptor-expressing (PD-1-expressing) B cells at the site of inflammation. Accumulation of memory B cells was mediated by CXCR3, evident by the observed increase in CXCR3-expressing synovial B cells compared with the periphery, differential regulation by key synovial cytokines, and restricted B cell invasion demonstrated in response to CXCR3 blockade.

The KIFC1 Kinesin Ensures the Fast Antibody Clearance Required for Parasite Infectivity.

Human innate immunity to involves the trypanosome C-terminal kinesin KIFC1, which transports internalized trypanolytic factor apolipoprotein L1 (APOL1) within the parasite. We show that KIFC1 preferentially associates with cholesterol-containing membranes and is indispensable for mammalian infectivity. Knockdown of KIFC1 did not affect trypanosome growth but rendered the parasites unable to infect mice unless antibody synthesis was compromised.

A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans.

T cells are classically recognized as distinct subsets that express αβ or γδ TCRs. We identify a novel population of T cells that coexpress αβ and γδ TCRs in mice and humans. These hybrid αβ-γδ T cells arose in the murine fetal thymus by day 16 of ontogeny, underwent αβ TCR-mediated positive selection into CD4+ or CD8+ thymocytes, and constituted up to 10% of TCRδ+ cells in lymphoid organs.

Low Density Granulocytes in ANCA Vasculitis Are Heterogenous and Hypo-Responsive to Anti-Myeloperoxidase Antibodies.

Low Density Granulocytes (LDGs), which appear in the peripheral blood mononuclear cell layer of density-separated blood, are seen in cancer, sepsis, autoimmunity, and pregnancy. Their significance in ANCA vasculitis (AAV) is little understood. As these cells bear the autoantigens associated with this condition and have been found to undergo spontaneous NETosis in other diseases, we hypothesized that they were key drivers of vascular inflammation.

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition).

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells.

Primary appendicular soft-tissue sarcoma resection: What tumour parameters affect wound closure planning?

Wound closure after wide, local excision of an appendicular soft-tissue sarcoma (STS) can be challenging. This study evaluates the value of magnetic resonance imaging (MRI)-based tumour parameters in planning wound closure. A total of 71 patients with a primary limb-based STS, excluding vascular or osseous involvement, excluding the shoulder or hand and hip or foot were included.

Differential Regulation of Human Treg and Th17 Cells by Fatty Acid Synthesis and Glycolysis.

In this study we examined the metabolic requirements of human T helper cells and the effect of manipulating metabolic pathways in Th17 and Treg cells. The Th17:Treg cell axis is dysregulated in a number of autoimmune or inflammatory diseases and therefore it is of key importance to identify novel strategies to modulate this axis in favor of Treg cells. We investigated the role of carbohydrate and fatty acid metabolism in the regulation of human memory T helper cell subsets, in order to understand how T cells are regulated at the site of inflammation where essential nutrients including oxygen may be limiting.