title: Upregulation and nuclear localization of TNF-like cytokine 1A (TL1A) and its receptors DR3 and DcR3 in psoriatic skin lesions.
abstract: TNF is critically involved in the pathogenesis of psoriasis. TL1A is a TNF-like cytokine, which, after binding to death domain receptor DR3, provides costimulatory signals to lymphocytes, amplifies Th1- and Th17-mediated immune responses and induces apoptotic cell death. These functions are inhibited when TL1A associates to decoy receptor DcR3. In the present study, we investigated the expression profiles for TL1A, DR3 and DcR3 in the normal skin and in psoriatic skin lesions. By use of immunohistochemistry, we were able to demonstrate constitutive cutaneous expression of DR3 and DcR3 but not of TL1A in healthy skin. On the other hand, in patients with active psoriasis, we observed abundant immunostaining for TL1A and significant upregulation of its receptors (P < 0.05 in comparison to healthy skin). TL1A, DR3 and DcR3 proteins, as well as mRNA transcripts reflecting in situ production of TL1A and DcR3, were also specifically increased in lesional as compared to non-lesional skin from patients with psoriasis (P < 0.05). These proteins were upregulated in cell populations that are critically involved in the pathogenesis of chronic skin inflammation, such as keratinocytes, macrophages in deep dermis and cells at the perivascular/endothelial area. Finally, we provide evidence for the existence of nuclear localization of TL1A in inflammatory cells from psoriatic lesions. This was also observed in inflamed synovia from patients with rheumatoid arthritis, but not in neoplastic TL1A-expressing cell lines. We conclude that interactions between TL1A and its two receptors may be involved in the pathogenesis of chronic skin inflammation that takes place in psoriasis.
authors.affiliation: 1st Department of Propaedeutic and Internal Medicine, Laikon Hospital, University of Athens Medical School, 17 Agiou Thoma street, Athens, Greece. gbamias@gmail.com
authors.forename: Giorgos
authors.initials: G
authors.lastname: Bamias
authors.forename: Kostas
authors.initials: K
authors.lastname: Evangelou
authors.forename: Theognosia
authors.initials: T
authors.lastname: Vergou
authors.forename: Katerina
authors.initials: K
authors.lastname: Tsimaratou
authors.forename: Garyfallia
authors.initials: G
authors.lastname: Kaltsa
authors.forename: Christina
authors.initials: C
authors.lastname: Antoniou
authors.forename: Athanasios
authors.initials: A
authors.lastname: Kotsinas
authors.forename: Sungee
authors.initials: S
authors.lastname: Kim
authors.forename: Vassilis
authors.initials: V
authors.lastname: Gorgoulis
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Stratigos
authors.forename: Petros P
authors.initials: PP
authors.lastname: Sfikakis
mesh_terms: D000328:Adult; D000368:Aged; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000235:genetics* / Q000378:metabolism*; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000235:genetics* / Q000378:metabolism*; D012867:Skin / Q000378:metabolism / Q000473:pathology; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D053219:Receptors, Tumor Necrosis Factor, Member 25; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C506033:TNFRSF25 protein, human; C505911:TNFRSF6B protein, human; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15