title: c-Jun N-terminal kinase (JNK)-phospho-c-JUN (ser63/73) pathway is essential for FOXP3 nuclear translocation in psoriasis.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Jinjin
authors.initials: J
authors.lastname: Wu
authors.forename: Wenying
authors.initials: W
authors.lastname: Ren
authors.forename: Xichuan
authors.initials: X
authors.lastname: Yang
authors.forename: Zhu
authors.initials: Z
authors.lastname: Shen
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D000873:Anthracenes / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D002648:Child; D003593:Cytoplasm / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000502:physiology; D011565:Psoriasis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D014466:Ultraviolet Rays; D055815:Young Adult
chemical_list: D000873:Anthracenes; D004791:Enzyme Inhibitors; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases