دورية أكاديمية
TWEAK functions with TNF and IL-17 on keratinocytes and is a potential target for psoriasis therapy.
| العنوان: | TWEAK functions with TNF and IL-17 on keratinocytes and is a potential target for psoriasis therapy. |
|---|---|
| المؤلفون: | Gupta RK; Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA., Gracias DT; Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA., Figueroa DS; Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA., Miki H; Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA., Miller J; Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA., Fung K; Bioinformatics Core, La Jolla Institute for Immunology, La Jolla, CA 92037, USA., Ay F; Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA., Burkly L; Biogen Inc., 115 Broadway, Cambridge, MA 02142, USA., Croft M; Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA. |
| المصدر: | Science immunology [Sci Immunol] 2021 Nov 19; Vol. 6 (65), pp. eabi8823. Date of Electronic Publication: 2021 Nov 19. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101688624 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2470-9468 (Electronic) Linking ISSN: 24709468 NLM ISO Abbreviation: Sci Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Association for the Advancement of Science, [2016]- |
| مواضيع طبية MeSH: | Cytokine TWEAK/*immunology , Interleukin-17/*immunology , Keratinocytes/*immunology , Psoriasis/*immunology , Tumor Necrosis Factors/*immunology, Animals ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Psoriasis/therapy |
| مستخلص: | TNF and IL-17 are two cytokines that drive dysregulated keratinocyte activity, and their targeting is highly efficacious in patients with psoriasis, but whether these molecules act with other inflammatory factors is not clear. Here, we show that mice having a keratinocyte-specific deletion of Fn14 ( Tnfrsf12a ), the receptor for the TNF superfamily cytokine TWEAK ( Tnfsf12 ), displayed reduced imiquimod-induced skin inflammation, including diminished epidermal hyperplasia and less expression of psoriasis signature genes. This corresponded with Fn14 being expressed in keratinocytes in human psoriasis lesions and TWEAK being found in several subsets of skin cells. Transcriptomic studies in human keratinocytes revealed that TWEAK strongly overlaps with IL-17A and TNF in up-regulating the expression of CXC chemokines, along with cytokines such as IL-23 and inflammation-associated proteins like S100A8/9 and SERPINB1/B9, all previously found to be highly expressed in the lesional skin of patients with psoriasis. TWEAK displayed strong synergism with TNF or IL-17A in up-regulating messenger RNA for many psoriasis-associated genes in human keratinocytes, including IL23A , IL36G , and multiple chemokines, implying that TWEAK acts with TNF and IL-17 to enhance feedback inflammatory activity. Correspondingly, therapeutic treatment of mice with anti-TWEAK was equally as effective as antibodies to IL-17A or TNF in reducing clinical and immunological features of psoriasis-like skin inflammation and combination targeting of TWEAK with either cytokine had no greater inhibitory effect, reinforcing the conclusion that all three cytokines function together. Thus, blocking TWEAK could be comparable to targeting TNF or IL-17 and might be considered as an alternate therapeutic treatment for psoriasis. |
| References: | J Allergy Clin Immunol. 2021 Feb;147(2):439-455. (PMID: 32560971) Cell Death Dis. 2018 Jul 23;9(8):801. (PMID: 30038329) Expert Opin Biol Ther. 2020 Jun;20(6):665-672. (PMID: 32045273) Nat Commun. 2013;4:1560. (PMID: 23463003) J Biol Chem. 1997 Dec 19;272(51):32401-10. (PMID: 9405449) Cytokine. 2021 Feb;138:155357. (PMID: 33153894) Nat Commun. 2017 May 22;8:15395. (PMID: 28530223) Immunol Rev. 2011 Nov;244(1):99-114. (PMID: 22017434) Mol Biol Rep. 2011 Jan;38(1):587-92. (PMID: 20358293) Curr Opin Immunol. 2017 Oct;48:99-107. (PMID: 28915378) Science. 2021 Jan 22;371(6527):. (PMID: 33479125) Exp Dermatol. 2016 Jan;25(1):32-7. (PMID: 26264384) Clin Ther. 2013 Aug;35(8):1137-49. (PMID: 23928094) Front Immunol. 2018 Jul 06;9:1549. (PMID: 30034395) Sci Rep. 2016 Apr 14;6:24477. (PMID: 27075414) J Invest Dermatol. 2011 Mar;131(3):677-87. (PMID: 21085185) Clin Cosmet Investig Dermatol. 2014 Sep 15;7:251-9. (PMID: 25246805) J Immunol. 2018 Sep 15;201(6):1605-1613. (PMID: 30181299) Exp Dermatol. 2012 Nov;21(11):822-6. (PMID: 22882537) J Invest Dermatol. 2015 Aug;135(8):1986-1995. (PMID: 25826425) J Eur Acad Dermatol Venereol. 2021 Apr;35(4):824-834. (PMID: 32790003) J Invest Dermatol. 2019 May;139(5):1110-1117. (PMID: 30684554) J Immunol. 2014 Nov 15;193(10):5140-8. (PMID: 25305315) Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6542-7. (PMID: 23576749) Front Immunol. 2019 Jul 26;10:1764. (PMID: 31402919) J Dermatolog Treat. 2017 Nov;28(7):606-612. (PMID: 28274164) Yale J Biol Med. 2020 Mar 27;93(1):97-110. (PMID: 32226340) Dermatology. 2019;235(2):91-100. (PMID: 30566935) Pharmacol Res. 2018 Mar;129:443-452. (PMID: 29155016) N Engl J Med. 2012 Mar 29;366(13):1190-9. (PMID: 22455413) Exp Dermatol. 2016 Dec;25(12):969-976. (PMID: 27305603) Genome Med. 2017 Mar 9;9(1):24. (PMID: 28279190) PLoS One. 2018 Oct 15;13(10):e0205340. (PMID: 30321197) J Allergy Clin Immunol. 2017 Sep;140(3):645-653. (PMID: 28887948) Ther Adv Chronic Dis. 2018 Aug;9(8):147-158. (PMID: 30065812) Front Immunol. 2021 Feb 12;11:599947. (PMID: 33643287) Mucosal Immunol. 2013 Nov;6(6):1131-42. (PMID: 23462911) Semin Immunol. 2014 Jun;26(3):229-36. (PMID: 24636536) PLoS One. 2008 Jul 16;3(7):e2737. (PMID: 18648529) Cytokine. 2021 Feb;138:155391. (PMID: 33302223) PLoS One. 2010 Apr 20;5(4):e10247. (PMID: 20422035) J Dermatol. 2021 Jun;48(6):722-731. (PMID: 33886133) J Invest Dermatol. 2019 Jul;139(7):1480-1489. (PMID: 30641038) Dermatol Ther. 2020 Nov;33(6):e14144. (PMID: 32761740) Expert Opin Biol Ther. 2018 Jun;18(6):605-607. (PMID: 29788767) BMC Immunol. 2021 Jan 28;22(1):11. (PMID: 33509093) J Am Acad Dermatol. 2014 Mar;70(3):512-6. (PMID: 24388724) Cytokine. 2016 Jan;77:10-3. (PMID: 26499979) Sci Rep. 2017 Dec 22;7(1):18045. (PMID: 29273799) Sci Rep. 2016 Jan 28;6:20134. (PMID: 26818707) Life Sci Alliance. 2020 Apr 28;3(6):. (PMID: 32345660) |
| معلومات مُعتمدة: | R01 AR072640 United States AR NIAMS NIH HHS |
| المشرفين على المادة: | 0 (Cytokine TWEAK) 0 (Il17a protein, mouse) 0 (Interleukin-17) 0 (Tnfsf12 protein, mouse) 0 (Tumor Necrosis Factors) |
| تواريخ الأحداث: | Date Created: 20211119 Date Completed: 20220307 Latest Revision: 20220520 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC8756771 |
| DOI: | 10.1126/sciimmunol.abi8823 |
| PMID: | 34797693 |
| قاعدة البيانات: | MEDLINE |
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