IFN-κ Is a Rheostat for Development of Psoriasiform Inflammation.
IFN-κ Is a Rheostat for Development of Psoriasiform Inflammation.
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DOI：
10.1016/j.jid.2021.05.029
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Kahlenberg JM
中科院分区：
文献类型：
--
作者：
Gharaee-Kermani M;Estadt SN;Tsoi LC;Wolf-Fortune SJ;Liu J;Xing X;Theros J;Reed TJ;Lowe L;Gruszka D;Ward NL;Gudjonsson JE;Kahlenberg JM
银屑病是一种常见的炎症性自身免疫性皮肤病。早期发现的干扰素-1签名发生在许多银屑病病变，但干扰素生产的来源仍然存在争议。IFN-κ是表皮中IFN-1产生的重要来源。我们确定了干扰素调节和银屑病相关基因在人类皮损的相关性。因此，我们希望使用充分表征的咪喹莫特银屑病模型来探索IFN-κ在银屑病中的作用。使用10周龄的三种小鼠品系：在表皮中过表达Ifnk的野生型C57 B1/6、C57 B1/6（即，转基因的），和全身IFN γ/IFN γ（即，敲除）菌株。通过在双耳上局部应用咪喹莫特连续8天来诱导银屑病。值得注意的是，皮肤病变和炎性细胞浸润的严重程度在转基因小鼠中比在野生型小鼠中比在基因敲除小鼠中更显著地增加。基因表达分析发现，与咪喹莫特治疗后的敲除小鼠相比，转基因小鼠中Mxa、Illb、Tnfa、Il 6、Il 12、Il 23、Il 17和Ifng的上调幅度大于野生型小鼠。此外，咪喹莫特增加CD 8+和CD 4 + T细胞浸润在转基因小鼠比野生型比敲除小鼠。总之，我们确定了IFN-κ作为一种变阻器启动银屑病样炎症。这表明在疾病早期靶向IFN-1可能是控制银屑病炎症的有效方法。
Psoriasis is a common, inflammatory autoimmune skin disease. Early detection of an IFN-1 signature occurs in many psoriasis lesions, but the source of IFN production remains debated. IFN-κ is an important source of IFN-1 production in the epidermis. We identified a correlation between IFN-regulated and psoriasis-associated genes in human lesional skin. We thus wanted to explore the effects of IFN-κ in psoriasis using the well-characterized imiquimod psoriasis model. Three mouse strains aged 10 weeks were used: wild-type C57Bl/6, C57Bl/6 that overexpress Ifnk in the epidermis (i.e., transgenic), and total body Ifnk‒/‒ (i.e., knockout) strain. Psoriasis was induced by topical application of imiquimod on both ears for 8 consecutive days. Notably, the severity of skin lesions and inflammatory cell infiltration was more significantly increased in transgenic than in wild-type than in knockout mice. Gene expression analysis identified greater upregulation of Mxa, Il1b, Tnfa, Il6, Il12, Il23, Il17, and Ifng in transgenic compared to wild-type compared to knockout mice after imiquimod treatment. Furthermore, imiquimod increased CD8+ and CD4+ T-cell infiltration more in transgenic than in wild-type than in knockout mice. In summary, we identified IFN-κ as a rheostat for initiation of psoriasiform inflammation. This suggests that targeting IFN-1s early in the disease may be an effective way of controlling psoriatic inflammation.
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影响因子：
2.3
作者：
Li, Yuanyuan;Song, Yueqi;Deng, Liehua
通讯作者：
Deng, Liehua
影响因子：
6.1
作者：
Li, Leng;Zhang, Hong-yu;Han, Ling
通讯作者：
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影响因子：
27.4
作者：
Sarkar MK;Hile GA;Tsoi LC;Xing X;Liu J;Liang Y;Berthier CC;Swindell WR;Patrick MT;Shao S;Tsou PS;Uppala R;Beamer MA;Srivastava A;Bielas SL;Harms PW;Getsios S;Elder JT;Voorhees JJ;Gudjonsson JE;Kahlenberg JM
通讯作者：
Kahlenberg JM
影响因子：
4.7
作者：
Eloranta, Maija-Leena;Ronnblom, Lars
通讯作者：
Ronnblom, Lars
局部咪喹莫德（Imiquimod）由于意外口服吸收而产生全身效应。
影响因子：
4.6
作者：
Grine L;Steeland S;Van Ryckeghem S;Ballegeer M;Lienenklaus S;Weiss S;Sanders NN;Vandenbroucke RE;Libert C
通讯作者：
Libert C