Upregulation of Interleukin-35 Subunits in Regulatory T Cells in a Murine Model of Allergic Rhinitis

Abstract

Objective: Regulatory T (Treg) cells play a critical role in the pathophysiology of allergic rhinitis (AR). We investigated the regulatory roles of interleukin (IL)-35, an immunosuppressive cytokine expressed by CD4⁺CD25⁺Foxp3⁺ Treg cells, in a murine model of AR. Methods: The expression of IL-35 subunits (Ebi3, encoded by Ebi3, and IL-12p35, encoded by IL12a) and IL-35 receptor chains (IL12rb and IL6st) in nasal mucosa and in spleen-derived Treg cells from ovalbumin (OVA)-sensitized AR was analyzed by immunohistochemistry and quantitative real-time RT-PCR techniques. Results: IL-35 subunit secretion was associated with local OVA sensitization in this murine model of AR. Ebi3 and IL-12p35, as well as CD3, were expressed differentially in the same regions of nasal mucosa of both AR and control animals. Ebi3 mRNA levels were significantly downregulated in the nasal mucosa of AR mice compared with control mice. Similarly, Ebi3 and IL12a mRNA levels were significantly upregulated in CD4⁺CD25⁺ Treg cells and, correspondingly, downregulated in CD4⁺CD25^- T effector (Teff) cells. IL6st mRNA levels were also significantly downregulated in CD4⁺CD25^- Teff cells. Conclusions: Decreased Ebi3 may have a crucial regulatory effect on the nasal mucosa in AR. The increased IL-35 subunit expression in CD4⁺CD25⁺ Treg cells may contribute to regulating the pathogenesis of AR. i 2014 S. Karger AG, Basel