Abstract
TIM4 (T cell immunoglobulin mucin domain molecule-4) plays a critical role in the initiation of skewed T helper (Th) 2 polarization. The factors regulating TIM4 expression are unclear. This study tests a hypothesis that p300 and STAT6 (signal transducer and activator transcription-6) regulates TIM4 expression in dendritic cells (DC). In this study, a food allergy mouse model was developed with ovalbumin (a specific antigen) and cholera toxin (CT; an adjuvant). The chromatin immunoprecipitation assay was performed to evaluate the chromatin changes at TIM4 and STAT6 promoters. The TIM4 expression was evaluated by real time RT-PCR and Western blotting. The results showed that high levels of p300 and TIM4 were detected in the intestinal DCs of mice with intestinal allergy. p300 is involved in the CT-induced TIM4 expression in DCs. p300 interacts with the chromatin at the TIM4 promoter locus in DCs isolated from allergic mice. CT increases p300 expression to regulate STAT6 levels in DCs. STAT6 mediates the CT-induced TIM4 expression in DCs. In conclusion, p300 and STAT6 mediate the microbial product CT-induced TIM4 expression in DCs.
Highlights
It is estimated that more than 20% population in the world are affected by allergic diseases[1]
The results showed higher levels of p300 and T cell immunoglobulin mucin domain molecule-4 (TIM4) in dendritic cells (DC) isolated from the small intestine of allergic mice as compared with that from the control mice (Fig. 1A–D)
The results showed the frequency of TIM4+ CD45.2+ signal transducer and activator transcription-6 (STAT6)− DCs was below the detectable levels, while about 30% TIM4+ DCs were detected in those CD45.2+ STAT6+ DCs (Fig. 5B,C), or the CD45.1+ DCs treated with control shRNA
Summary
It is estimated that more than 20% population in the world are affected by allergic diseases[1]. P300 is associated with allergic diseases, such as Cui et al reported that the p300-induced histone acetylation played a critical role in the induction of Th2 polarization in airway allergy[10]. The signal transducer and activator transcription-6 (STAT6) is another important factor in the development of allergic reactions[11]. This protein plays a central role in exerting IL-4, the signature cytokine of Th2 responses, mediated biological responses. Based on the above information, we hypothesize that p300 and STAT6 modulate the expression of TIM4 in DCs. The results of the present study showed that the exposure to CT, one of the microbial products often used in the development of allergic disease animal models, significantly increased www.nature.com/scientificreports/. The expression of TIM4 in DCs, in which both p300 and STAT6 were associated with the regulation of TIM4 gene transcription
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