Interleukin-6 (IL-6) is a cytokine that plays a crucial role in the immune system. It is produced by a wide range of cells, including macrophages, dendritic cells, T cells, B cells, and fibroblasts. IL-6 has been shown to be involved in the response to both infectious and non-infectious stimuli, including allergens.
Allergens are substances that can trigger an allergic response in susceptible individuals. Allergic reactions are mediated by the immune system, which recognizes the allergen as foreign and mounts an immune response against it. This immune response is characterized by the activation of immune cells, the production of antibodies, and the release of cytokines such as IL-6.
IL-6 is produced in response to the detection of pathogen-associated molecular patterns (PAMPs) contained in allergens. PAMPs are molecules that are unique to pathogens and are recognized by the immune system as foreign. PAMPs are recognized by pattern recognition receptors (PRRs) expressed by immune cells, including Toll-like receptors (TLRs) and NOD-like receptors (NLRs).
TLRs are a family of PRRs that are located on the cell surface and in endosomes. TLRs recognize a wide range of PAMPs, including bacterial lipopolysaccharides (LPS), flagellin, and viral RNA. When TLRs recognize their ligands, they initiate a signaling cascade that leads to the activation of transcription factors such as NF-κB and IRF3. These transcription factors induce the expression of cytokines such as IL-6.
NLRs are another family of PRRs that are located in the cytoplasm. NLRs recognize intracellular PAMPs such as bacterial peptidoglycan and viral RNA. When NLRs recognize their ligands, they recruit and activate caspase-1, which cleaves pro-IL-1β and pro-IL-18 to their active forms. In addition to IL-1β and IL-18, caspase-1 also cleaves pro-IL-6 to its active form.
IL-6 has been shown to play a crucial role in the response to allergens. IL-6 is involved in the activation of T cells, the differentiation of B cells into plasma cells, and the production of antibodies. IL-6 is also involved in the recruitment of immune cells to the site of allergen exposure, including neutrophils and eosinophils. IL-6 has been shown to be elevated in the serum and bronchoalveolar lavage fluid of patients with allergic asthma, suggesting that IL-6 may play a role in the pathogenesis of this disease.
In addition to its role in the immune response to allergens, IL-6 has been implicated in a variety of other physiological processes. IL-6 is involved in the regulation of the acute phase response, which is a systemic response to infection, injury, or inflammation characterized by the production of a variety of cytokines, acute phase proteins, and other molecules. IL-6 is a major mediator of this response, and it has been shown to induce the production of acute phase proteins such as C-reactive protein and fibrinogen.
IL-6 is also involved in the regulation of hematopoiesis, which is the process of blood cell formation. IL-6 has been shown to be a potent stimulator of the proliferation and differentiation of hematopoietic stem cells and progenitor cells, leading to the production of a variety of blood cell types, including red blood cells, platelets, and immune cells.
IL-6 has been implicated in the pathogenesis of a variety of diseases, including rheumatoid arthritis, multiple myeloma, and certain types of cancer. In rheumatoid arthritis, IL-6 is thought to contribute to the inflammation and joint destruction characteristic of the disease. IL-6 is also involved in the growth and survival of multiple myeloma cells, and it has been targeted for therapeutic purposes in this disease. In cancer, IL-6 has been shown to promote tumor growth and metastasis, and it has been targeted as a potential therapeutic target in certain types of cancer.
In a new study the researchers have found that Defective interleukin-6 (IL-6) signaling has been associated with Th2 bias and elevated IgE levels.
Defective interleukin-6 (IL-6) signaling has been associated with Th2 bias and elevated IgE levels. However, the underlying mechanism by which IL-6 prevents the development of Th2-driven diseases remains unknown. Using a model of house dust mite (HDM)-induced Th2 cell differentiation and allergic airway inflammation, we showed that IL-6 signaling in allergen-specific T cells was required to prevent Th2 cell differentiation and the subsequent IgE response and allergic inflammation.
Th2 cell lineage commitment required strong sustained IL-2 signaling. We found that IL-6 turned off IL-2 signaling during early T-cell activation and thus inhibited Th2 priming.
Mechanistically, IL-6-driven inhibition of IL-2 signaling in responding T cells was mediated by upregulation of Suppressor Of Cytokine Signaling 3 (SOCS3). This mechanism could be mimicked by pharmacological Janus Kinase-1 (JAK1) inhibition.
Collectively, our results identify an unrecognized mechanism that prevents the development of unwanted Th2 cell responses and associated diseases and outline potential preventive interventions.
reference link : https://www.nature.com/articles/s41423-023-01012-1