IL17RC Gene

The IL17RC gene (IL17RC stands for "Interleukin 17 Receptor C") is a protein-coding gene located on chromosome 3p25.3. The protein produced by the IL17RC gene is found in many tissue types of the body and is involved in cell signaling as part of the IL-17 pathway. Together with the protein produced by the IL17RA gene, it forms one of several receptors for IL-17 cytokines. Several alternatively spliced transcript variants encoding different isoforms have been discovered for the gene.

The IL17RC gene encodes a single-pass type I membrane protein that shares similarities with the interleukin-17 receptor (IL-17RA). Unlike IL-17RA, a receptor protein that is predominantly expressed in hematopoietic cells and binds with high affinity only to IL-17A, this receptor protein is expressed in non-hematopoietic tissues. It binds both IL-17A and IL-17F with similar affinity.

The protein encoded by the IL17RC gene functions as a receptor for IL17A and IL17F, both important effector cytokines of the innate and adaptive immune systems involved in antimicrobial host defense and maintenance of tissue integrity. IL17A and IL17F are important effector cytokines of the innate and adaptive immune systems involved in antimicrobial host defense and maintenance of tissue integrity.

The receptors for IL17A and IL17F form homodimers as part of a heterodimeric complex with IL17RA. Binding of IL17A-IL17F to the heterodimeric IL17RA-IL17RC receptor complex triggers a homotypic interaction of the IL17RA and IL17RC chains with the TRAF3IP2 adaptor via SEFIR domains. This leads to downstream TRAF6-mediated activation of NF-kappa-B and MAPkinase signaling pathways, ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides, and matrix metalloproteinases, which can lead to a strong immune response.

Among other things, there is activation and recruitment of neutrophils at sites of infection and inflammation. Furthermore, production of the antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells is stimulated, preventing microbial invasion through the epithelial barrier.

Induces transcriptional activation of IL33, a potent cytokine that stimulates group 2 innate lymphoid cells and adaptive T helper 2 cells involved in the allergic response to fungi in the lung.

Diseases associated with IL17RC include:

• CMC, familial type 9 (= Chronic mucocutaneous candidiasis, familial CAND9)
• Thoracic ossification of the posterior longitudinal ligament (T-OPLL) can cause thoracic spinal stenosis leading to incurable myelopathy and radiculopathy. The etiology of T-OPLL is unknown and the disease is difficult to treat surgically. Whole genome sequencing identified a genetic variant at rs199772854 of the interleukin-17 receptor C gene (IL17RC) as a potentially pathogenic locus associated with T-OPLL (Wang P et al. 2019).

Associated signaling pathways include cytokine signaling pathways and cytokine expression by Th17 cells.

1. Ho AW et al. (2010) IL-17RC is required for immune signaling via an extended SEF/IL-17R signaling domain in the cytoplasmic tail. J Immune 185: 1063-1070.
2. Kawaguchi Y (2022) Biomarker Research Approach to the Pathogenesis of Ossification of the Spinal Ligament: A Review. Spine Surg Relat Res 6:224-232.
3. Ling Y et al. (2015) Inherited IL-17RC deficiency in patients with chronic mucocutaneous candidiasis. J Exp Med212: 619-631.
4. Wang P et al. (2019) IL17RC affects the predisposition to thoracic ossification of the posterior longitudinal ligament. J Orthop Surg Res 14:210.