Correlation Engine 2.0
Clear Search sequence regions


In some psoriatic patients, impaired function of FOXP3+ regulatory T cells has been identified without well-uncovered mechanism(s). Meanwhile, dysregulation of FOXP3 nuclear translocation has been observed in some autoimmune syndromes and in some cancer cells. To investigate whether there is dysregulation of FOXP3 nuclear translocation in some psoriatic patients and to explore the signal pathway responsible for FOXP3 nuclear translocation. CD4+CD25+ T cells were purified from peripheral blood mononuclear cells by magnetic-bead-based method. FOXP3 expression pattern in psoriasis was analyzed by immunohistochemical staining. Transient and stable cell lines were established by exogenous construct transfection and retrovirus infection respectively. Cytoplasmic and nuclear FOXP3 was analyzed by immunoprecipitation, western blot and immunofluorescence. We observed that some psoriatic patients showed cytoplasmic retention of FOXP3 and these patients had higher serum IL-17 and disease severity. We found that c-Jun N-terminal kinase (JNK) was essential to FOXP3 nuclear translocation. Inhibition of JNK pathway caused cytoplasmic retention of FOXP3. This inhibition could also impair the promotion of FOXP3 nuclear translocation by UVB. Next we found that phospho-c-JUN (ser63/73), main downstream of JNK pathway, could interact with FOXP3 and promoted FOXP3 nuclear translocation. Our study demonstrated that JNK-phospho-c-JUN (ser63/73) pathway was essential for FOXP3 nuclear translocation in psoriasis. Our study suggested selective manipulation of JNK in Tregs seems to be a promising choice for the development of drugs in the treatment of autoimmune inflammatory diseases. Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Citation

Ling Chen, Jinjin Wu, Wenying Ren, Xichuan Yang, Zhu Shen. c-Jun N-terminal kinase (JNK)-phospho-c-JUN (ser63/73) pathway is essential for FOXP3 nuclear translocation in psoriasis. Journal of dermatological science. 2013 Feb;69(2):114-21

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 23182477

View Full Text