Abstract
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.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
