IL17B - interleukin 17B |Elisa - Clia - Antibody - Protein

Background

Interleukin 17B (IL-17B) is part of the broader IL-17 cytokine family, which plays a crucial role in immune responses, particularly in inflammation and host defense mechanisms. The IL-17 family is known for its involvement in mediating pro-inflammatory responses, and IL-17B is no exception, being linked to various inflammatory processes. IL-17B was discovered relatively recently compared to other interleukins, and while its functions overlap with other IL-17 family members, it has distinct roles in certain pathological conditions.

IL-17B, similar to its counterparts such as IL-17A and IL-17F, is produced by different types of immune and non-immune cells. It interacts with specific receptors to modulate immune cell activities and contribute to both normal immune responses and the pathology of diseases characterized by chronic inflammation, like cancer, autoimmune diseases, and inflammatory bowel disease.

IL-17B signals primarily through the IL-17 receptor B (IL-17RB), which is distinct from the receptors used by other IL-17 family members like IL-17A and IL-17F. This specific receptor-ligand interaction underlies the unique biological functions of IL-17B. Research on IL-17B is still developing, but evidence suggests it plays a role in tissue inflammation, mucosal immunity, and oncogenesis, making it a cytokine of interest for therapeutic interventions targeting inflammation-related diseases.

Protein Structure

IL-17B, like other members of the IL-17 family, is a small protein with distinct structural features that allow it to mediate its functions through receptor binding and subsequent activation of intracellular signaling pathways. The protein structure of IL-17B can be described as follows:

• Amino Acid Composition: IL-17B consists of 180 amino acids with a molecular weight of approximately 20.5 kDa. This relatively small size is typical of cytokines, allowing them to act as soluble signaling molecules.
• Secondary and Tertiary Structure: IL-17B is characterized by a four-helix bundle structure, which is a common motif in cytokines. This helical configuration is critical for maintaining its stability and enabling interactions with its receptor, IL-17RB. The IL-17 family is known to form disulfide-linked homodimers, a structural feature that enhances the cytokine's stability and receptor affinity. This dimerization is also essential for the functional interaction with the IL-17RB receptor.
• Receptor Binding Domain: IL-17B has specific regions responsible for binding to IL-17RB. The structural interface between IL-17B and its receptor allows it to induce signal transduction pathways that activate downstream effects, such as the production of pro-inflammatory cytokines. The precise molecular interactions between IL-17B and IL-17RB are crucial for its biological functions, which include promoting inflammation and influencing immune responses.
• Post-Translational Modifications: Like many cytokines, IL-17B may undergo post-translational modifications, such as glycosylation, which can influence its stability, bioavailability, and receptor interaction. These modifications are important for the proper folding and function of the cytokine, although specific modifications for IL-17B have yet to be thoroughly characterized.

Classification and Subtypes

IL-17B is part of the IL-17 family, which comprises six cytokines: IL-17A, IL-17B, IL-17C, IL-17D, IL-17E (also known as IL-25), and IL-17F. These cytokines are related based on their sequence homology and structural similarities, particularly the four-helix bundle structure and their ability to form homodimers.

• IL-17 Family Overview:
• IL-17A: Known for its role in autoimmunity and chronic inflammation.
• IL-17F: Similar to IL-17A, often co-expressed and plays a role in inflammatory responses.
• IL-17C: Plays a role in epithelial defense and barrier immunity.
• IL-17D: The least studied member, with roles in immune homeostasis.
• IL-17E (IL-25): Promotes Th2-type immune responses, important in allergic diseases.

IL-17B is distinguished from other family members by its specific receptor binding (IL-17RB) and its role in promoting tissue-specific inflammation and interacting with non-immune cells such as fibroblasts and epithelial cells.

Function and Biological Significance

The biological functions of IL-17B are centered around its role in modulating immune and inflammatory responses, particularly in tissues. While IL-17A and IL-17F are primarily associated with immune cell activation and pathogen defense, IL-17B has been shown to be involved in epithelial cell responses and tissue inflammation.

Functions:

1. Pro-inflammatory Role: IL-17B is a pro-inflammatory cytokine that, upon binding to its receptor IL-17RB, induces the production of other inflammatory mediators such as TNF-α, IL-6, and MCP-1. These molecules contribute to local inflammation by recruiting immune cells, such as macrophages and neutrophils, to the site of inflammation or tissue damage.
2. Tissue-Specific Inflammation: IL-17B is produced not only by immune cells but also by epithelial cells, fibroblasts, and other non-immune cells. This indicates its role in maintaining tissue integrity and mediating inflammatory responses in organs such as the gut, lungs, and skin. This tissue-specific action differentiates it from IL-17A and IL-17F, which are more broadly involved in systemic inflammation.
3. Interaction with IL-17RB: The receptor IL-17RB, which is highly expressed in epithelial tissues, mediates IL-17B's effects. The activation of IL-17RB triggers downstream signaling pathways, such as NF-κB and MAPK, leading to increased expression of pro-inflammatory cytokines, chemokines, and antimicrobial peptides. This makes IL-17B an important player in mucosal immunity.
4. Role in Oncogenesis: Recent studies suggest that IL-17B may contribute to tumorigenesis by promoting cancer cell survival and tumor growth. In particular, elevated levels of IL-17B and its receptor IL-17RB have been observed in certain cancers, such as breast cancer. IL-17B may promote a tumor-supportive microenvironment by increasing inflammation, angiogenesis, and resistance to apoptosis in tumor cells.

Biological Significance:

IL-17B's role in tissue inflammation and its interactions with epithelial and non-immune cells highlight its significance in mucosal immunity and organ-specific inflammation. In contrast to other IL-17 family members, which are primarily produced by immune cells, IL-17B’s expression in non-immune cells points to a role in local tissue regulation. It acts as a bridge between immune and non-immune cells, ensuring an adequate response to damage or infection while also playing a role in tissue homeostasis.

IL-17B's involvement in cancer biology adds another layer of significance, as it is increasingly recognized as a contributor to the tumor microenvironment, particularly in promoting inflammation-driven tumor progression.

Clinical Issues

Given its role in inflammation and tissue-specific responses, IL-17B has been implicated in several inflammatory diseases and cancers. Dysregulation of IL-17B signaling can contribute to pathological inflammation, autoimmunity, and tumor growth, making it a potential target for therapeutic intervention.

Diseases Associated with IL-17B:

1. Inflammatory Bowel Disease (IBD): IL-17B is expressed in the gut and contributes to the chronic inflammation observed in conditions like Crohn’s disease and ulcerative colitis. Its role in maintaining epithelial integrity while promoting inflammation suggests that IL-17B may be involved in the persistent mucosal damage seen in these disorders.
2. Cancer: Elevated IL-17B expression has been detected in several cancers, including breast cancer and pancreatic cancer. IL-17B promotes tumor growth by enhancing inflammation, promoting cell survival, and increasing angiogenesis. The IL-17B/IL-17RB axis is particularly important in tumor-associated inflammation, making it a potential target for anti-cancer therapies.
3. Autoimmune Diseases: Due to its ability to induce inflammatory cytokines, IL-17B is likely involved in autoimmune diseases characterized by chronic inflammation, such as rheumatoid arthritis and psoriasis. Blocking IL-17B signaling may help alleviate inflammation in these conditions.
4. Chronic Respiratory Diseases: In conditions such as asthma and chronic obstructive pulmonary disease (COPD), IL-17B is thought to contribute to airway inflammation and remodeling. It enhances the production of inflammatory cytokines and chemokines in the airway epithelium, driving chronic respiratory inflammation.

Therapeutic Potential:

Given its role in promoting inflammation and its contribution to tumor progression, IL-17B and its receptor IL-17RB are being investigated as potential therapeutic targets. IL-17RB antagonists may be useful in treating cancers where IL-17B is overexpressed. Additionally, anti-IL-17B therapies could be beneficial in treating chronic inflammatory diseases and autoimmunity.

Summary

IL-17B is a pro-inflammatory cytokine within the IL-17 family that plays an essential role in tissue-specific inflammation, mucosal immunity, and cancer biology. It signals through IL-17RB, leading to the activation of downstream pathways that induce the production of inflammatory mediators. While IL-17B is similar to other IL-17 family members in its ability to drive inflammation, it is unique in its expression patterns and specific roles in epithelial and fibroblast-mediated responses. Clinically, IL-17B is implicated in diseases such as inflammatory bowel disease, cancer, and chronic inflammatory conditions, making it a promising target for therapeutic intervention in these areas. Further research into IL-17B’s specific mechanisms and its role in disease pathology could lead to novel treatments for both inflammatory diseases and cancer.