IL17D - interleukin 17D |Elisa - Clia - Antibody - Protein

Background

Interleukin 17D (IL-17D) is a member of the IL-17 cytokine family, which plays a crucial role in modulating the immune response, particularly in inflammation and host defense. The IL-17 family consists of six cytokines (IL-17A through IL-17F), all of which are involved in regulating immune responses, especially those associated with infection, autoimmunity, and tissue inflammation. IL-17D is one of the less well-characterized members of this family, but it is known to have distinct roles in the regulation of innate immunity, particularly in the induction of inflammatory cytokines in various tissues.

Unlike the more widely studied IL-17A and IL-17F, which are produced by Th17 cells and have well-established roles in inflammatory diseases, the function of IL-17D has only recently come to light. It is expressed in a variety of non-hematopoietic cells, including fibroblasts, endothelial cells, and smooth muscle cells, where it acts to modulate immune responses by inducing the production of inflammatory cytokines and recruiting immune cells. The expression of IL-17D is induced in response to stress signals, tissue injury, and infection, suggesting a role in the early stages of immune responses.

Protein Structure

IL-17D, like other IL-17 family cytokines, is a small glycoprotein. It has a molecular weight of approximately 20-25 kDa, consistent with other cytokines in its family. Structurally, IL-17D shares the common features of the IL-17 family, including:

• Amino Acid Composition: IL-17D is composed of around 202 amino acids and contains conserved cysteine residues that are critical for maintaining its tertiary structure. These residues participate in disulfide bonds, which help stabilize the overall structure of the protein.
• Four-Helix Bundle: Similar to other members of the IL-17 family, IL-17D adopts a four-helix bundle conformation, a structural motif critical for cytokine function. This four-helix bundle is responsible for the protein's stability and its ability to interact with specific receptors on the surface of target cells.
• Homodimerization: IL-17D is believed to form homodimers, which is characteristic of the IL-17 family. This dimerization is facilitated by the disulfide bonds and is crucial for receptor binding and signal transduction. Homodimerization enhances the cytokine’s functional activity, increasing its binding affinity for receptors and enabling it to exert biological effects.
• Receptor Binding: IL-17D primarily signals through the IL-17 receptor family, particularly IL-17RD, though detailed receptor interaction mechanisms are not as fully elucidated as those of other IL-17 cytokines like IL-17A or IL-17F. Receptor engagement triggers downstream signaling cascades that are responsible for inducing inflammatory responses.
• Post-Translational Modifications: Although specific post-translational modifications (PTMs) such as glycosylation or phosphorylation of IL-17D have not been comprehensively studied, PTMs are common in cytokines and likely play a role in regulating IL-17D’s stability, secretion, and activity.

Classification and Subtypes

IL-17D belongs to the IL-17 cytokine family, which is known for its involvement in promoting inflammation and modulating both innate and adaptive immune responses. This family includes:

• IL-17A and IL-17F: Key drivers of autoimmune diseases such as psoriasis, rheumatoid arthritis, and multiple sclerosis.
• IL-17B: Implicated in chronic inflammation and certain cancers.
• IL-17C: Involved in mucosal immunity and epithelial cell defense.
• IL-17E (IL-25): Promotes Th2-type immune responses, playing a role in allergic conditions.
• IL-17D: The least studied family member but recognized for its role in modulating the immune response by inducing cytokine production and promoting inflammation.

IL-17D does not have any well-defined subtypes but is classified within the pro-inflammatory cytokine group. While it is similar to other IL-17 cytokines in structure, its specific functions and receptor interactions distinguish it within the family.

Function and Biological Significance

IL-17D plays a role in promoting inflammation and recruiting immune cells to sites of infection or injury. It is produced primarily by non-immune cells, such as fibroblasts, endothelial cells, and smooth muscle cells, and is released in response to cellular stress, damage, or infection.

Functions:

1. Induction of Inflammatory Cytokines: One of the primary functions of IL-17D is the induction of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF). These cytokines are critical for the recruitment and activation of immune cells, including neutrophils and macrophages, at the site of infection or tissue damage.
2. Promotion of Antiviral and Antimicrobial Responses: By inducing cytokine production and recruiting immune cells, IL-17D helps orchestrate the body's early responses to viral and bacterial infections. This contributes to the activation of the innate immune system, enhancing the clearance of pathogens.
3. Recruitment of Innate Immune Cells: IL-17D can indirectly recruit innate immune cells, including neutrophils and natural killer (NK) cells, by inducing the production of chemokines such as CXCL1, CXCL8 (IL-8), and CCL2 (MCP-1). These chemokines help guide immune cells to sites of infection or inflammation, where they can eliminate pathogens and initiate tissue repair processes.
4. Role in Tumor Immunity: Emerging evidence suggests that IL-17D may play a role in tumor immunity. It has been shown to promote the recruitment of NK cells to the tumor microenvironment, where they can target and eliminate tumor cells. IL-17D expression in tumors has been associated with enhanced antitumor immune responses, suggesting that it may have therapeutic potential in cancer immunotherapy.

Biological Significance:

IL-17D serves as an important regulator of inflammatory responses in tissues, particularly in the context of innate immunity. Its ability to induce cytokine production and recruit immune cells makes it a critical player in the body's defense against infections and injuries. Furthermore, IL-17D may have unique roles in modulating immune responses within the tumor microenvironment, positioning it as a potential therapeutic target for cancer treatment.

Clinical Issues

Although IL-17D is not as widely studied as other IL-17 family members, its role in inflammation and immunity suggests that dysregulation of IL-17D could be implicated in a variety of diseases, including autoimmune disorders, inflammatory diseases, and cancer.

Diseases Associated with IL-17D:

1. Inflammatory and Autoimmune Diseases: Given IL-17D’s role in promoting inflammation, it may contribute to the pathogenesis of chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, and multiple sclerosis. In these conditions, excessive or dysregulated cytokine production leads to tissue damage and chronic inflammation.
2. Infections: IL-17D plays a protective role in the immune response to infections by inducing pro-inflammatory cytokines and recruiting immune cells. Deficiencies in IL-17D production could impair the immune response to bacterial and viral pathogens, making individuals more susceptible to infection.
3. Cancer: IL-17D has been implicated in the regulation of tumor immunity. Studies have shown that IL-17D can promote the recruitment of NK cells to tumors, enhancing antitumor immune responses. Low levels of IL-17D expression in certain cancers have been associated with poor prognosis, suggesting that IL-17D may have protective effects against tumor progression. Conversely, in some cancers, IL-17D may promote tumor-associated inflammation, which could facilitate tumor growth and metastasis.

Therapeutic Potential:

The modulation of IL-17D activity holds potential for therapeutic applications in inflammatory diseases and cancer. Inhibiting IL-17D signaling may be beneficial in conditions where excessive inflammation is harmful, such as autoimmune disorders. On the other hand, boosting IL-17D expression or activity could enhance antitumor immune responses, making it a potential target for cancer immunotherapy.

Summary

IL-17D is a member of the IL-17 cytokine family that plays a significant role in inflammatory responses and innate immunity. It is primarily expressed by non-hematopoietic cells such as fibroblasts and endothelial cells and functions to induce the production of inflammatory cytokines and recruit immune cells to sites of infection or tissue injury. Although less well-characterized than other IL-17 cytokines, IL-17D has important roles in promoting antimicrobial responses and regulating tumor immunity.

Dysregulation of IL-17D has been linked to various inflammatory diseases, autoimmune disorders, and cancers, where it contributes to chronic inflammation and may influence the immune response to tumors. Given its dual role in promoting inflammation and enhancing antitumor immunity, IL-17D represents an intriguing target for therapeutic intervention in both inflammatory diseases and cancer.