The present invention relates ZcytoR21 antagonists, such as soluble receptors and anti-ZcytoR21 antibodies, that are useful in blocking, inhibiting, reducing, antagonizing or neutralizing the activity of IL-17C. IL-17C is a cytokine that is involved in inflammatory processes and human disease. ZcytoR21 is a receptor for IL-17C. The present invention includes soluble ZcytoR21, anti-ZcytoR21 antibodies and binding partners, as well as methods for antagonizing IL-17C using such soluble receptors, antibodies and binding partners.