IL-10Rα, or Interleukin-10 Receptor Alpha, is a crucial component of the IL-10 receptor complex, playing a significant role in immune regulation. This receptor binds to IL-10, an anti-inflammatory cytokine, and mediates its signaling through a series of downstream pathways that influence immune homeostasis and inflammatory responses. Primarily expressed on hematopoietic cells like monocytes, macrophages, and certain T-cells, IL-10Rα’s functions have made it an important target in understanding and potentially treating immune-related diseases.1,2
History of IL-10Rα Discovery
The IL-10 cytokine was first described by Fiorentino and colleagues in 1989 as a factor that inhibited cytokine synthesis, initially termed “cytokine synthesis inhibitory factor”3. Following this, research identified the IL-10 receptor complex, including IL-10Rα, which is unique to IL-10 and essential for its immunosuppressive actions. Structural studies, such as those involving cryo-electron microscopy, have since elucidated the detailed assembly of IL-10 with IL-10Rα and IL-10Rβ, facilitating therapeutic development of IL-10 variants that can selectively engage IL-10Rα to modulate immune responses.3, 4
What Does IL-10Rα Stand For?
IL-10Rα stands for “Interleukin-10 Receptor Alpha.” It is part of a heterotetrameric receptor complex that includes two IL-10Rα subunits and two IL-10Rβ subunits. IL-10Rα serves as the primary ligand-binding unit, responsible for high-affinity interactions with IL-102, 3. IL-10Rα can form homodimers which play an important role in immune regulation.
What Do IL-10Rα Proteins Do?
IL-10Rα proteins are essential for initiating IL-10 signaling, which is critical for regulating inflammation. When IL-10 binds to IL-10Rα, the receptor complex recruits IL-10Rβ, triggering downstream signaling through the JAK-STAT pathway. This pathway, particularly involving STAT3, plays a key role in limiting pro-inflammatory cytokine production and reducing immune cell activation, thereby maintaining immune balance.1, 4
Function and Importance of the IL-10Rα Protein
IL-10Rα is essential in various physiological and pathological immune responses:
Anti-inflammatory Role:
IL-10Rα mediates IL-10’s suppressive effects on immune cells, particularly macrophages and monocytes, inhibiting their production of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β. This regulatory effect is crucial in preventing excessive inflammation and tissue damage, especially in autoimmune and chronic inflammatory diseases.1, 4
Role in Gut Homeostasis:
IL-10Rα is critical for maintaining mucosal immunity in the gut. Deficiencies in IL-10R signaling have been linked to severe inflammatory bowel disease (IBD), particularly in early-onset cases. Both murine and human studies show that IL-10Rα expression is essential for limiting intestinal inflammation and promoting immune tolerance in the gut.2
Neuroprotective Functions:
Research has demonstrated that intact IL-10Rα signaling protects against neuroinflammation and related neuronal damage in models of neurotropic viral infections. Blockade of IL-10Rα increases inflammatory damage, underscoring its potential protective role in the central nervous system.1
Clinical and Therapeutic Applications
Due to its central role in immune regulation, IL-10Rα has become a target for various therapeutic approaches aimed at enhancing or modulating IL-10’s effects:
Anti-inflammatory Therapy:
Recombinant IL-10 and IL-10 analogs are being explored as therapies for inflammatory conditions, with IL-10Rα as a critical component in achieving targeted immune suppression. Understanding IL-10Rα’s structure has allowed for the development of IL-10 variants with selective activity, designed to enhance anti-inflammatory responses without triggering unwanted immune activation.3, 4
Potential in Infectious Disease:
Given IL-10Rα’s ability to dampen inflammation, therapies that leverage its pathway may reduce pathology in diseases characterized by hyperinflammatory states, such as COVID-19. IL-10 modulation may help in managing “cytokine storms” by curbing excessive immune responses that lead to severe complications.4
Special Characteristics of IL-10Rα
IL-10Rα has unique characteristics that distinguish it from other cytokine receptors:
Selective Expression:
While IL-10Rα is predominantly expressed in immune cells, its expression can be upregulated in response to inflammatory stimuli, enhancing IL-10’s regulatory effects as needed. This adaptability is beneficial in contexts requiring rapid immune modulation.2
Structural Specificity:
IL-10Rα binds specifically to IL-10, whereas its co-receptor IL-10Rβ is shared among other type II cytokines like IL-22 and IL-26. This specificity allows IL-10Rα to direct IL-10 signaling to distinct immune regulatory pathways, limiting the potential for cross-reactive effects.3
A highly purified IIL10α dimer recombinant protein can significantly enhance the binding of IL-10 cytokine compared to the IL10Rα monomer protein
IL10Rα ectodomain is responsible for binding to the IL-10 cytokine. The use of IL10Rα dimer proteins in bioassays is a powerful strategy for studying immune responses, cytokine signaling, and receptor-ligand interactions. Conigen Bioscience has engineered IL10Rα dimer protein containing its ectodomain fused with a dimeric motif at the C-terminus to mimic the natural dimer. The highly purified IIL10α dimer recombinant protein can significantly enhance the binding of IL-10 cytokine compared to the IL10Rα monomer protein. By mimicking the natural dimer, IL10Rα is essential for understanding IL-10 receptor function in bioassays, particularly in studying IL-10 binding, signaling, and developing therapeutics.
Other Notable Names
IL-10Rα is also referred to as IL-10RA or IL10R1 in some literature. These names reflect its primary role as the alpha subunit of the IL-10 receptor complex and help distinguish it from IL-10Rβ, which functions as a secondary signaling partner.4
References
- Uhde, A-K., Ciurkiewicz, M., Herder, V., et al. (2018). Intact interleukin-10 receptor signaling protects from hippocampal damage elicited by experimental neurotropic virus infection of SJL mice. Scientific Reports, 8(6106). https://doi.org/10.1038/s41598-018-24378-z.
- Shouval, D. S., Ouahed, J., Biswas, A., et al. (2014). Interleukin 10 Receptor Signaling: Master Regulator of Intestinal Mucosal Homeostasis in Mice and Humans. Advances in Immunology, 122, 177–210. https://doi.org/10.1016/B978-0-12-800267-4.00005-5.
- Saxton, R. A., Tsutsumi, N., Su, L. L., et al. (2021). Structure-based decoupling of the pro- and anti-inflammatory functions of interleukin-10. Science, 371(6535). https://doi.org/10.1126/science.abc8433.
- Carlini, V., Noonan, D. M., Abdalalem, E., et al. (2023). The multifaceted nature of IL-10: Regulation, role in immunological homeostasis and its relevance to cancer, COVID-19, and post-COVID conditions. Frontiers in Immunology, 14, 1161067. https://doi.org/10.3389/fimmu.2023.1161067.
