Interleukin 4 ≈ Interleukin 4
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Absence of Tumor Necrosis Factor Supports Alternative Activation of Macrophages in the Liver after Infection with Leishmania major Open
The absence of tumor necrosis factor (TNF) causes lethal infection by Leishmania major in normally resistant C57BL/6J (B6.WT) mice. The underlying pathogenic mechanism of this fatal disease has so far remained elusive. We found that B6.WT …
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Tuning the Cytokine Responses: An Update on Interleukin (IL)-4 and IL-13 Receptor Complexes Open
Interleukin (IL)-4 and IL-13 are related cytokines that regulate many aspects of allergic inflammation. They play important roles in regulating the responses of lymphocytes, myeloid cells, and non-hematopoietic cells. In T-cells, IL-4 indu…
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Interleukin-18 in Health and Disease Open
Interleukin (IL)-18 was originally discovered as a factor that enhanced IFN-γ production from anti-CD3-stimulated Th1 cells, especially in the presence of IL-12. Upon stimulation with Ag plus IL-12, naïve T cells develop into IL-18 recepto…
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Identification of a T follicular helper cell subset that drives anaphylactic IgE Open
Thirteen is the charm in anaphylaxis Immunoglobulin E (IgE) is a type of antibody associated with allergies and response to parasites such as worms. When high-affinity, allergen-specific IgE binds its target, it can cross-link receptors on…
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Dual blockade of IL‐4 and IL‐13 with dupilumab, an IL‐4Rα antibody, is required to broadly inhibit type 2 inflammation Open
Background Dupilumab, a fully human monoclonal antibody that binds IL‐4Rα and inhibits signaling of both IL‐4 and IL‐13, has shown efficacy across multiple diseases with underlying type 2 signatures and is approved for treatment of asthma,…
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IL4-driven microglia modulate stress resilience through BDNF-dependent neurogenesis Open
Hippocampal microglia mediate stress resilience.
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Unique Action of Interleukin-18 on T Cells and Other Immune Cells Open
Interleukin (IL)-18 was originally discovered as a factor that enhances interferon (IFN)-γ production by anti-CD3-stimulated Th1 cells, particularly in association with IL-12. IL-12 is a cytokine that induces development of Th1 cells. IL-1…
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JAK–STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review Open
Atopic dermatitis (AD) is a chronic, inflammatory, pruritic form of dermatosis with heterogeneous manifestations that can substantially affect patients' quality of life. AD has a complex pathogenesis, making treatment challenging for derma…
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Tumor promoting roles of IL-10, TGF-β, IL-4, and IL-35: Its implications in cancer immunotherapy Open
Cytokines play a critical role in regulating host immune response toward cancer and determining the overall fate of tumorigenesis. The tumor microenvironment is dominated mainly by immune-suppressive cytokines that control effector antitum…
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Human IFN-γ immunity to mycobacteria is governed by both IL-12 and IL-23 Open
Human IFN-γ–dependent immunity to mycobacteria is less compromised in IL-12Rβ2 or IL-23R deficiency than IL-12Rβ1 deficiency.
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IL-33, IL-25, and TSLP induce a distinct phenotypic and activation profile in human type 2 innate lymphoid cells Open
Key Points IL-25, IL-33, and TSLP induce distinct activation profiles in ILC2s. IL-2 further amplifies their response and induces an NK-like phenotype. ILC2 plasticity is observed in serum-free media even when in the presence of IL-25, IL-…
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STAT6 Upregulation Promotes M2 Macrophage Polarization to Suppress Atherosclerosis Open
BACKGROUND Macrophages are highly heterogeneous and plastic cells that are involved in all stages of atherogenesis. They can undergo polarization by shifting between M1 and M2 functional phenotypes. However, the role of macrophage polariza…
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The Metabolic Requirements of Th2 Cell Differentiation Open
Upon activation, naïve CD4+ T cells differentiate into a number of specialized T helper (Th) cell subsets. Th2 cells are central players in immunity to helminths and are implicated in mediating the inflammatory pathology associated with al…
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Blocking Interleukin (IL)4- and IL13-Mediated Phosphorylation of STAT6 (Tyr641) Decreases M2 Polarization of Macrophages and Protects Against Macrophage-Mediated Radioresistance of Inflammatory Breast Cancer Open
These data suggest that inhibition of M2 polarization of macrophages by PM37 can prevent radioresistance of IBC by down-regulating PRKCZ.
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Basophil Recruitment into Tumor-Draining Lymph Nodes Correlates with Th2 Inflammation and Reduced Survival in Pancreatic Cancer Patients Open
In pancreatic ductal adenocarcinomas (PDAC), lymphoid infiltrates, comprised mainly of Th2 cells, predict a poor survival outcome in patients. IL4 signaling has been suggested to stabilize the Th2 phenotype in this setting, but the cellula…
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Interleukin‐31 and interleukin‐31 receptor: New therapeutic targets for atopic dermatitis Open
Atopic dermatitis ( AD ) is characterized by chronic, eczematous, severe pruritic skin lesions caused by skin barrier dysfunction and T helper (Th)2 cell‐mediated immunity. Interleukin ( IL )‐31 is a potent pruritogenic cytokine primarily …
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IL-33/IL-31 Axis in Immune-Mediated and Allergic Diseases Open
Several allergic and immunologic diseases including asthma, food allergy (FA), chronic spontaneous urticaria (CSU), atopic dermatitis (AD), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), and Behçet…
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Regulation of Skin Barrier Function via Competition between AHR Axis versus IL-13/IL-4‒JAK‒STAT6/STAT3 Axis: Pathogenic and Therapeutic Implications in Atopic Dermatitis Open
Atopic dermatitis (AD) is characterized by skin inflammation, barrier dysfunction, and chronic pruritus. As the anti-interleukin-4 (IL-4) receptor α antibody dupilumab improves all three cardinal features of AD, the type 2 cytokines IL-4 a…
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Expanding Diversity in Molecular Structures and Functions of the IL-6/IL-12 Heterodimeric Cytokine Family Open
The interleukin (IL)-6/IL-12 family cytokines have pleiotropic functions and play critical roles in multiple immune responses. This cytokine family has very unique characteristics in that they comprise two distinct subunits forming a heter…
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CD5L Promotes M2 Macrophage Polarization through Autophagy-Mediated Upregulation of ID3 Open
CD5L (CD5 molecule-like) is a secreted glycoprotein that controls key mechanisms in inflammatory responses, with involvement in processes such as infection, atherosclerosis, and cancer. In macrophages, CD5L promotes an anti-inflammatory cy…
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IL-4 Receptor Alpha Signaling through Macrophages Differentially Regulates Liver Fibrosis Progression and Reversal Open
Alternative (M2-type) macrophage activation through IL-4Rα promotes liver inflammation and fibrosis progression but speeds up fibrosis reversal. This demonstrates context dependent, opposing roles of M2-type macrophages. During reversal IL…
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TSLP signaling in CD4 <sup>+</sup> T cells programs a pathogenic T helper 2 cell state Open
The cytokine TSLP promotes the generation of a pathogenic T cell subset that exacerbates allergic responses.
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Role of IL-35 in sublingual allergen immunotherapy Open
IL-35 and iTR35 cells are potential novel immune regulators induced by SLIT. The clinical relevance of SLIT can be underscored by restoration of protective iTR35 cells.
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IL-21 is a broad negative regulator of IgE class switch recombination in mouse and human B cells Open
IgE antibodies may elicit potent allergic reactions, and their production is tightly controlled. The tendency to generate IgE has been thought to reflect the balance between type 1 and type 2 cytokines, with the latter promoting IgE. Here,…
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Human germline heterozygous gain-of-function <i>STAT6</i> variants cause severe allergic disease Open
STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with …
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An Update on Interleukin-9: From Its Cellular Source and Signal Transduction to Its Role in Immunopathogenesis Open
Interleukin-9 (IL-9) is a pleiotropic cytokine and was primarily studied in the context of T helper 2 (TH2)-associated immuno-pathological conditions such as asthma and parasitic infections. There was a paradigm shift in the biology of IL-…
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Targeting IL-4 for the Treatment of Atopic Dermatitis Open
Atopic dermatitis (AD) is an immune-mediated inflammatory skin disease characterized by a predominant type 2 immune response. Type 2 immunity is driven by multiple cytokines, including interleukin (IL)‑4 and IL-13 that are considered centr…
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NLRP3-Dependent and -Independent Processing of Interleukin (IL)-1β in Active Ulcerative Colitis Open
A contributing factor in the development of ulcerative colitis (UC) and Crohn’s disease (CD) is the disruption of innate and adaptive signaling pathways due to aberrant cytokine production. The cytokine, interleukin (IL)-1β, is highly infl…
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The immunosuppressive cytokine interleukin-4 increases the clonogenic potential of prostate stem-like cells by activation of STAT6 signalling Open
Interleukin-4 plays a critical role in the regulation of immune responses and has been detected at high levels in the tumour microenvironment of cancer patients, where concentrations correlate with the grade of malignancy. In prostate canc…
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IL-13/STAT6 signaling plays a critical role in the epithelial-mesenchymal transition of colorectal cancer cells Open
Colorectal cancer (CRC) is one of the most common causes of cancer-related death worldwide due to the distant metastases. Compelling evidence has reported that epithelial-mesenchymal transition (EMT) is involved in promoting cancer invasio…