IL-2 family cytokines IL-9 and IL-21 differentially regulate innate and adaptive type 2 immunity in asthma.

Background: Asthma is often accompanied by type 2 immunity rich in IL-4, IL-5, and IL-13 cytokines produced by T2 lymphocytes or type 2 innate lymphoid cells (ILC2s). IL-2 family cytokines play a key role in the differentiation, homeostasis, and effector function of innate and adaptive lymphocytes.

Objective: IL-9 and IL-21 boost activation and proliferation of T2 and ILC2s, but the relative importance and potential synergism between these γ common chain cytokines are currently unknown.

Keratinocytes activated by IL-4/IL-13 express IL-2Rγ with consequences on epidermal barrier function.

Atopic dermatitis (AD) is a Th2-type inflammatory disease characterized by an alteration of epidermal barrier following the release of IL-4 and IL-13. These cytokines activate type II IL-4Rα/IL-13Rα1 receptors in the keratinocyte. Whilst IL-2Rγ, that forms type I receptor for IL-4, is only expressed in haematopoietic cells, recent studies suggest its induction in keratinocytes, which questions about its role.

IL-17 and IL-22 are pivotal cytokines to delay wound healing of infected skin.

Introduction: Although the presence of pathogens in skin wounds is known to delay the wound healing process, the mechanisms underlying this delay remain poorly understood. In the present study, we have investigated the regulatory role of proinflammatory cytokines on the healing kinetics of infected wounds.

Methods: We have developed a mouse model of cutaneous wound healing, with or without wound inoculation with and , two major pathogens involved in cutaneous wound bacterial infections.

Chilblains observed during the COVID-19 pandemic cannot be distinguished from classic, cold-related chilblains.

Background: Type 1 interferon (IFN-I) response induced by SARS-CoV-2 has been hypothesized to explain the association between chilblain lesions (CL) and SARS-CoV-2 infection.

Objective: To explore direct cytopathogenicity of SARS-CoV-2 in CL and to focus on IFN-I expression in patients with chilblains.

Materials & Methods: A monocentric cohort of 43 patients presenting with CL from April 2020 to May 2021 were included.

JAK/STAT: Why choose a classical or an alternative pathway when you can have both?

A subset of cytokines triggers the JAK-STAT pathway to exert various functions such as the induction of inflammation and immune responses. The receptors for these cytokines are dimers/trimers of transmembrane proteins devoid of intracellular kinase activity. Instead, they rely on Janus kinases (JAKs) for signal transduction.

Development of SARS-CoV2 humoral response including neutralizing antibodies is not sufficient to protect patients against fatal infection.

More than a year after the start of the pandemic, COVID-19 remains a global health emergency. Although the immune response against SARS-CoV-2 has been extensively studied, some points remain controversial. One is the role of antibodies in viral clearance and modulation of disease severity.

Inflammation-Induced Coagulopathy Substantially Differs Between COVID-19 and Septic Shock: A Prospective Observational Study.

Critical COVID-19, like septic shock, is related to a dysregulated systemic inflammatory reaction and is associated with a high incidence of thrombosis and microthrombosis. Improving the understanding of the underlying pathophysiology of critical COVID-19 could help in finding new therapeutic targets already explored in the treatment of septic shock. The current study prospectively compared 48 patients with septic shock and 22 patients with critical COVID-19 regarding their clinical characteristics and outcomes, as well as key plasmatic soluble biomarkers of inflammation, coagulation, endothelial activation, platelet activation, and NETosis.

Blocking GARP-mediated activation of TGF-β1 did not alter innate or adaptive immune responses to bacterial infection or protein immunization in mice.

Transmembrane protein GARP binds latent TGF-β1 to form GARP:(latent)TGF-β1 complexes on the surface of several cell types including Tregs, B-cells, and platelets. Upon stimulation, these cells release active TGF-β1. Blocking TGF-β1 activation by Tregs with anti-GARP:TGF-β1 mAbs overcomes resistance to PD1/PD-L1 blockade and induces immune-mediated regressions of murine tumors, indicating that Treg-derived TGF-β1 inhibits anti-tumor immunity.

Rotavirus susceptibility of antibiotic-treated mice ascribed to diminished expression of interleukin-22.

The commensal microbiota regulates susceptibility to enteric pathogens by fine-tuning mucosal innate immune responses, but how susceptibility to enteric viruses is shaped by the microbiota remains incompletely understood. Past reports have indicated that commensal bacteria may either promote or repress rotavirus replication in the small intestine of mice. We now report that rotavirus replicated more efficiently in the intestines of germ-free and antibiotic-treated mice compared to animals with an unmodified microbiota.

A Targetable, Noncanonical Signal Transducer and Activator of Transcription 3 Activation Induced by the Y-Less Region of IL-22 Receptor Orchestrates Imiquimod-Induced Psoriasis-Like Dermatitis in Mice.

Exacerbated IL-22 activity induces tissue inflammation and immune disorders such as psoriasis. However, because IL-22 is also essential for tissue repair and defense at barrier interfaces, targeting IL-22 activity to treat psoriasis bears the risk of deleterious effects at mucosal sites such as the gut. We previously showed in vitro that IL-22 signaling relies on IL-22 receptor alpha (IL-22Rα) Y-dependent and -independent pathways.

New insight in understanding the contribution of SGLT1 in cardiac glucose uptake: evidence for a truncated form in mice and humans.

Although sodium glucose cotransporter 1 (SGLT1) has been identified as one of the major SGLT isoforms expressed in the heart, its exact role remains elusive. Evidence using phlorizin, the most common inhibitor of SGLTs, has suggested its role in glucose transport. However, phlorizin could also affect classical facilitated diffusion via glucose transporters (GLUTs), bringing into question the relevance of SGLT1 in overall cardiac glucose uptake.

Selective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains.

The transcription factor STAT3 is frequently activated in human solid and hematological malignancies and remains a challenging therapeutic target with no approved drugs to date. Here, we develop synthetic antibody mimetics, termed monobodies, to interfere with STAT3 signaling. These monobodies are highly selective for STAT3 and bind with nanomolar affinity to the N-terminal and coiled-coil domains.

Loss of NFKB1 Results in Expression of Tumor Necrosis Factor and Activation of Signal Transducer and Activator of Transcription 1 to Promote Gastric Tumorigenesis in Mice.

Background & Aims: Activity of nuclear factor κB transcription factors and signaling via signal transducer and activator of transcription (STAT) are frequently altered in gastric cancer cells. Mice lacking NFKB1 (Nfkb1 mice) develop invasive gastric cancer, and their gastric tissues have increased levels of cytokines, such as interleukin (IL) 6, IL22, IL11, and tumor necrosis factor (TNF), as well as increased activation of STAT1. We investigated whether these cytokines were required for STAT1 activation in gastric tissues of mice and critical for gastric tumorigenesis.

Microenvironmental Th9 and Th17 lymphocytes induce metastatic spreading in lung cancer.

Immune microenvironment plays a critical role in lung cancer control versus progression and metastasis. In this investigation, we explored the effect of tumor-infiltrating lymphocyte subpopulations on lung cancer biology by studying in vitro cocultures, in vivo mouse models, and human lung cancer tissue. Lymphocyte conditioned media (CM) induced epithelial-mesenchymal transition (EMT) and migration in both primary human lung cancer cells and cell lines.

Ozone-Induced Aryl Hydrocarbon Receptor Activation Controls Lung Inflammation via Interleukin-22 Modulation.

Airborne ozone exposure causes severe lung injury and inflammation. The aryl hydrocarbon Receptor (AhR) (1), activated in pollutant-induced inflammation, is critical for cytokine production, especially IL-22 and IL-17A. The role of AhR in ozone-induced lung inflammation is unknown.

IL-9 exerts biological function on antigen-experienced murine T cells and exacerbates colitis induced by adoptive transfer.

IL-9 is involved in various T cell-dependent inflammatory models including colitis, encepahlitis, and asthma. However, the regulation and specificity of IL-9 responsiveness by T cells during immune responses remains poorly understood. Here, we addressed this question using two different models: experimental colitis induced by transfer of naive CD4 CD45RB T cells into immunodeficient mice, and OVA-specific T cell activation.

IL-24 contributes to skin inflammation in Para-Phenylenediamine-induced contact hypersensitivity.

Para-Phenylenediamine (PPD) is an aromatic amine used in hair dyes and in temporary black henna tattoos, which is a frequent cause of allergic contact dermatitis (ACD). ACD is a skin inflammatory reaction characterized by modifications such as spongiosis, exocytosis and acanthosis. The aim of this study is to characterize the expression and the role of IL-20-related cytokines, including IL-19, IL-20, IL-22 and IL-24, in ACD.

Endogenous IL-22 is dispensable for experimental glomerulonephritis.

In recent years, the cytokine interleukin (IL)-22 attracted considerable attention due to its important immunoregulatory function in barrier tissues, such as the gut, lung, and skin. Although a regenerative role of IL-22 in renal tubular damage has been demonstrated, the role of IL-22 in the immunopathogenesis of glomerular injury is still unknown. Here, we demonstrate that the IL-22 receptor is expressed in the glomerular compartment of the kidney and that IL-22 expression increases in the renal cortex after induction of glomerular injury in a mouse model for crescentic glomerulonephritis (cGN, nephrotoxic nephritis).

Increased expression of interleukin-9 in patients with allergic contact dermatitis caused by p-phenylenediamine.

Background: Allergic contact dermatitis has been described as a type IV reaction caused by antigen-specific T cells. Central roles for CD8 cytotoxic T cells as effector cells and CD4 T cells as regulatory cells have been suggested. T helper (Th) 2 and Th1 cytokines have been implicated; however, the nature of the allergen influences the Th response.

The TLR7 ligand R848 prevents mouse graft--host disease and cooperates with anti-interleukin-27 antibody for maximal protection and regulatory T-cell upregulation.

In spite of considerable therapeutic progress, acute graft--host disease still limits allogeneic hematopoietic cell transplantation. We recently reported that mouse infection with nidovirus lactate dehydrogenase elevating virus impairs disease in non-conditioned B6D2F1 recipients of parental B6 spleen cells. As this virus activates TLR7, we tested a pharmacological TLR7 ligand, R848, in this model and observed complete survival if donor and recipients were treated before transplantation.

Interleukin-22 level is negatively correlated with neutrophil recruitment in the lungs in a Pseudomonas aeruginosa pneumonia model.

Pseudomonas aeruginosa is a major threat for immune-compromised patients. Bacterial pneumonia can induce uncontrolled and massive neutrophil recruitment ultimately leading to acute respiratory distress syndrome and epithelium damage. Interleukin-22 plays a central role in the protection of the epithelium.

Limited Presence of IL-22 Binding Protein, a Natural IL-22 Inhibitor, Strengthens Psoriatic Skin Inflammation.

Psoriasis is a chronic inflammatory disease resulting from dysregulated immune activation associated with a large local secretion of cytokines. Among them, IL-22 largely contributes to epithelial remodeling and inflammation through inhibiting the terminal differentiation of keratinocytes and inducing antimicrobial peptides and selected chemokines. The activity of IL-22 is regulated by IL-22 binding protein (IL-22BP); however, the expression and role of IL-22BP in psoriatic skin has remained unknown so far.