Skin expression of IL-23 drives the development of psoriasis and psoriatic arthritis in mice

CHEN, LILI; SMALDINI, PAOLA; GULKO, PERCIO ; DESHPANDE, MADHURA ; GARCIA, ROBERTO; LIRA, SERGIO A.; GRISOTTO, MARCOS; HE, ZHENGXIANG; FURTADO, GLAUCIA C.

Scientific Reports

Nature Publishing Group

Lugar: Londres; Año: 2020 vol. 10

Psoriasis(PS) is a chronic skin inflammation. Up to 30% of the patients with PS develop psoriaticarthritis (PsA), a condition characterized by inflammatory arthritis thataffects joints or entheses. Although there is mounting evidence for a criticalrole of interleukin-23 (IL-23) signaling in the pathogenesis of both PS and PsA,it remains unclear whether IL-23-induced skin inflammation drives jointdisease. Here, we show that mice expressing increased levels of IL-23 in theskin (K23 mice) develop a PS-likedisease that is characterized by acanthosis, parakeratosis, hyperkeratosis, andinflammatory infiltrates in the dermis. Skin disease preceded development of PsA,including enthesitis, dactylitis, and bone destruction. The development ofenthesitis and dactylitis was not due to high circulating levels of IL-23, astransgenic animals and controls had similar levels of this cytokine incirculation. IL-22, a downstream cytokine of IL-23, was highly increased in theserum of K23 mice. Although IL-22deficiency did not affect skin disease development, IL-22 deficiency aggravatedthe PsA-like disease in K23 mice. Ourresults demonstrate a central role for skin expressed IL-23 in the initiation ofPS and on pathogenic processes leading to PsA. <!-- /* Font Definitions */ @font-face{font-family:"MS Mincho";panose-1:2 2 6 9 4 2 5 8 3 4;mso-font-alt:"ＭＳ 明朝";mso-font-charset:128;mso-generic-font-family:modern;mso-font-pitch:fixed;mso-font-signature:-536870145 1791491579 134217746 0 131231 0;}@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Tahoma;panose-1:2 11 6 4 3 5 4 4 2 4;mso-font-charset:0;mso-generic-font-family:swiss;mso-font-pitch:variable;mso-font-signature:-520081665 -1073717157 41 0 66047 0;}@font-face{font-family:"@MS Mincho";panose-1:2 2 6 9 4 2 5 8 3 4;mso-font-charset:128;mso-generic-font-family:modern;mso-font-pitch:fixed;mso-font-signature:-536870145 1791491579 134217746 0 131231 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0in;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Tahoma",sans-serif;mso-fareast-font-family:"MS Mincho";mso-fareast-theme-font:minor-fareast;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-fareast-language:JA;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:"Cambria",serif;mso-ascii-font-family:Cambria;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"MS Mincho";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Cambria;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-fareast-language:JA;}size:8.5in 11.0in;margin:1.0in 1.0in 1.0in 1.0in;mso-header-margin:.5in;mso-footer-margin:.5in;mso-paper-source:0;}div.WordSection1{page:WordSection1;}