IL10RA - Interleukin 10 Receptor Alpha | Elisa - Clia - Antibody - Protein

Background:

Interleukin-10 (IL-10) is a cytokine, secreted by various immune cells such as T cells, B cells, macrophages, and dendritic cells. It is produced as a homodimer, meaning it consists of two identical subunits linked together. Each subunit contains about 160 amino acids and adopts a tertiary structure stabilized by disulfide bonds. IL-10 exerts its effects by binding to specific cell surface receptors, including the IL-10 receptor (IL-10R), which initiates downstream signaling pathways. IL-10 is primarily known for its anti-inflammatory properties. It suppresses the activity of pro-inflammatory cytokines and immune cells, thereby dampening the inflammatory response. IL-10 inhibits the production of cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and interferon-gamma (IFN-γ), which are involved in inflammation and immune activation. IL-10 plays a crucial role in regulating immune responses to pathogens and preventing excessive tissue damage caused by inflammation. It helps to maintain immune homeostasis by limiting the duration and intensity of immune responses, thereby preventing autoimmune reactions and tissue injury. IL-10 also promotes tissue repair and regeneration by reducing inflammation and promoting wound healing. It also contributes to the induction of immune tolerance, allowing the immune system to differentiate between harmless antigens and potential threats, thereby preventing autoimmune diseases. IL-10RA is a critical component of the IL-10 receptor complex, which also includes the IL-10 receptor subunit beta (IL-10RB).Upon ligand binding, IL-10 induces conformational changes in the IL-10 receptor complex, leading to the activation of intracellular signaling pathways. IL-10RB plays a crucial role in transmitting these signals, particularly through the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway.

Protein Structure:

IL10RA is a type I transmembrane protein comprising 578 amino acids. The protein includes:

• Extracellular Domain: This domain contains two fibronectin type III-like domains responsible for binding IL-10.
• Transmembrane Domain: Anchors the receptor to the cell membrane.
• Intracellular Domain: Essential for signal transduction, interacting with downstream signaling molecules.

Classification and Subtypes:

IL10RA is part of the class II cytokine receptor family, which includes receptors for various other cytokines like IL-22 and IL-26. IL10RA forms a receptor complex with IL-10 receptor beta (IL10RB), another subunit necessary for IL-10 signal transduction.

Function and Biological Significance:

• IL-10 Binding: IL10RA specifically binds to IL-10 with high affinity. Upon binding IL-10, IL10RA associates with IL10RB to form a functional signaling receptor complex.
• Signal Transduction: The IL-10/IL10RA/IL10RB complex activates the JAK-STAT signaling pathway, particularly STAT3, leading to the transcription of anti-inflammatory and immunoregulatory genes.
• Immune Regulation: By mediating IL-10's effects, IL10RA helps regulate immune responses, reducing the production of pro-inflammatory cytokines and promoting the development and function of regulatory T cells (Tregs).

Interactions:

• IL10RB: The interaction between IL10RA and IL10RB is essential for IL-10-mediated signal transduction.
• JAK-STAT Pathway: IL10RA is linked with the activation of Janus kinases (JAK1 and TYK2) and Signal Transducers and Activators of Transcription (STAT3), crucial for propagating IL-10's anti-inflammatory signals.
• Immune Cells: IL10RA interacts with various immune cells to modulate their activity, suppressing excessive inflammatory responses and promoting immune tolerance.

Clinical Issues:

• Genetic Mutations: Mutations in the IL10RA gene can lead to early-onset inflammatory bowel disease (IBD) and other autoimmune disorders due to impaired IL-10 signaling.
• Autoimmune Diseases: Deficient IL10RA signaling is associated with heightened inflammatory responses, contributing to autoimmune pathologies.
• Therapeutic Target: Targeting IL10RA or enhancing its function holds potential in treating autoimmune and inflammatory diseases by restoring proper immune regulation.

Summary:

IL10RA (Interleukin 10 Receptor Alpha) is a vital receptor for the anti-inflammatory cytokine IL-10, playing a crucial role in immune regulation and the suppression of inflammation. By forming a receptor complex with IL10RB and activating the JAK-STAT signaling pathway, IL10RA mediates IL-10's effects, promoting immune homeostasis and preventing excessive inflammatory responses. Mutations or deficiencies in IL10RA are linked to various autoimmune and inflammatory diseases, highlighting its significance in health and disease. Understanding IL10RA's function and interactions provides valuable insights for developing therapeutic strategies to modulate immune responses and treat related disorders.