Structure and Cellular Sources

• Interleukin-10 (IL-10) is a cytokine with potent anti-inflammatory properties, composed of 178 amino acids in the form of a homodimer.
• Identified in 1989 as cytokine synthesis inhibitory factor (CSIF).
• Secreted by several immune cells: T regulatory cells (Tregs), T helper 2 cells, macrophages, dendritic cells, and B cells.
• Contains six α-helices folded in a compact V-shaped structure required for receptor interaction and biological activity.
• Structural framework well preserved during evolution, highlighting its significance in immune regulation.

Signalling Mechanisms and Regulation

• IL-10 activates its receptor, a complex system including IL-10R1 (alpha chain) and IL-10R2 (beta chain).
• Binding to its receptor leads to activation of the JAK-STAT signalling pathway, with STAT3 as the major effector, along with some STAT1 and STAT5.
• Results in the expression of genes responsible for inhibiting inflammatory processes.
• Production regulated at transcriptional, post-transcriptional, and epigenetic levels.
• Modulated by cytokines, pathogens, and environmental cues to allow optimal immune responses while avoiding excessive inflammation.

Immunoregulatory Functions

• IL-10 regulates the immune response through multiple pathways:
• Inhibits synthesis of pro-inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6, IL-12) in macrophages and dendritic cells.
• Decreases costimulatory molecule and MHC class II on antigen-presenting cells (APCs).
• Enhances B cell survival, proliferation, and antibody secretion, especially IgA important for mucosal immunity.
• Supports development and function of regulatory T cells while suppressing effector T cell responses.
• Essential for preventing excessive immune responses and maintaining tissue homeostasis.

Role in Disease and Pathology

• Lack of IL-10 signalling linked to inflammatory bowel diseases, particularly early-onset colitis.
• In autoimmune diseases, affected IL-10 signalling leads to enhanced inflammation and tissue damage.
• Some pathogens and tumors exploit IL-10 to escape immune responses, promoting persistent infection or immune evasion.
• Elevated IL-10 in chronic infections can suppress protective immune responses.
• Cancer cells upregulate IL-10 production, creating an immunosuppressive environment that promotes tumor growth and metastasis.

Therapeutic Applications and Future Perspectives

• Recombinant IL-10 tested for inflammatory disorders (e.g., inflammatory bowel disease, rheumatoid arthritis), but systemic administration has shown mixed results.
• Focus on developing more precise delivery methods, including cell-specific carriers and modified IL-10 with enhanced therapeutic characteristics.
• In cancer immunotherapy, strategies aimed at suppressing IL-10 signalling to boost anti-tumor immune responses.
• IL-10-producing regulatory B cells being investigated as potential cellular therapies for autoimmune diseases.

Suitable ELISA Kits

• IL-10 ELISA Kit
• Interleukin-10 ELISA Kit