Abstract
Regulation of transcription factors like NF-κB decides about type and strength of developing inflammatory and immune responses. CYLD acts as a negative regulatory element of NF-κB activation, however the naturally occurring short splice variant CYLDEx7/8 (sCYLD) has positive regulatory properties. An exclusively expression of sCYLD leads to a hyperactive phenotype of dendritic cells (DC) and increased numbers of long living antibody secreting B cells. In the present study we investigated the function of sCYLD on T cells in a murine model of allergic airway disease. Following sensitization and challenge towards the model antigen Ovalbumin (OVA), wild type (WT) and animals with a T cell specific expression of CYLDEx7/8 (CyldFL*CD4cre) were analyzed for the induction of an allergic airway disease. 48 hours following the last challenge animals with exclusively T cells expressing sCYLD demonstrating increased numbers of eosinophils in BAL, enhanced inflammation in the lung and increased numbers of goblet cells in comparison to WT animals. Moreover the T cell specific sCYLD expression leads to increased secretion of total IgE and all classes of antigen specific immunoglobulines were clearly upregulated in comparison to sensitized and challenged WT. These data suggest that CYLD plays an important role in the regulation of T cell responses. Beside the modulation of DC and B cell the short splice variant of CYLD affects also T cells and seems to induce a hyper responsive T cell phenotype. This work provides a new few in T cell regulation and underlines the important role of CYLD and T cells for the induction of allergic responses.
- © 2011 ERS