IL-21 Attenuates FITC-Induced Contact Hypersensitivity Response via Regulation of Dendritic Cell Function

IL-21 is mainly produced by activated CD4⁺ T cells and is involved in the activation of immune cells such as T cells and macrophages. In contrast, IL-21 suppresses dendritic cell maturation. We studied the effect of IL-21 in a mouse model of FITC-induced contact hypersensitivity using IL-21 isoform transgenic (IL-21iso-Tg) mice. Tissue inflammation at 24 hours after elicitation in IL-21iso-Tg mice was significantly weaker than that in wild-type mice. In agreement with tissue inflammation, recruitment of CD4⁺ and CD8⁺ T cells, neutrophils, and macrophages into the inflamed tissue was decreased in IL-21iso-Tg mice. In addition, both mRNA expression and protein production of inflammatory cytokines were lower in IL-21iso-Tg mice. In the skin, T cells were activated at inducible skin-associated lymphoid tissue, which is likely a gut-associated lymphoid tissue. The mRNA level of CXCL2, an essential chemokine for inducible skin-associated lymphoid tissue formation, was significantly lower in IL-21iso-Tg mice, and histological analysis showed that dendritic cell clustering, a preliminary step in inducible skin-associated lymphoid tissue formation, was impaired. Our study showed that IL-21 down-regulated inducible skin-associated lymphoid tissue formation and reduced contact hypersensitivity response.