{"entity": "publication", "iuid": "f3beeb0dee2148e8a216209728227595", "timestamp": "2026-09-23T21:35:42.888Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f3beeb0dee2148e8a216209728227595.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f3beeb0dee2148e8a216209728227595"}}, "title": "Cross-talk between IFN-\u03b3 and TWEAK through miR-149 amplifies skin inflammation in psoriasis.", "authors": [{"family": "Srivastava", "given": "Ankit", "initials": "A"}, {"family": "Luo", "given": "Longlong", "initials": "L"}, {"family": "Lohcharoenkal", "given": "Warangkana", "initials": "W"}, {"family": "Meisgen", "given": "Florian", "initials": "F"}, {"family": "Pasquali", "given": "Lorenzo", "initials": "L"}, {"family": "Pivarcsi", "given": "Andor", "initials": "A"}, {"family": "Sonkoly", "given": "Enik\u00f6", "initials": "E"}], "type": "journal article", "published": "2021-06-00", "journal": {"title": "J. Allergy Clin. Immunol.", "issn": "1097-6825", "volume": "147", "issue": "6", "pages": "2225-2235", "issn-l": "0091-6749"}, "abstract": "Psoriasis is a chronic inflammatory skin disease with disturbed interplay between immune cells and keratinocytes. A strong IFN-\u03b3 signature is characteristic for psoriasis skin, but the role of IFN-\u03b3 has been elusive. MicroRNAs are short RNAs regulating gene expression.\n\nOur aim was to investigate the role of miR-149 in psoriasis and in the inflammatory responses of keratinocytes.\n\nmiR-149 expression was measured by quantitative RT-PCR in keratinocytes isolated from healthy skin and lesional and nonlesional psoriasis skin. Synthetic miR-149 was injected intradermally into the back skin of mice, and imiquimod was applied to induce psoriasis-like skin inflammation, which was then evaluated at the morphologic, histologic, and molecular levels. miR-149 was transiently overexpressed or inhibited in keratinocytes in combination with IFN-\u03b3- and/or TNF-related weak inducer of apoptosis (TWEAK)-treatment.\n\nHere we report a microRNA-mediated mechanism by which IFN-\u03b3 primes keratinocytes to inflammatory stimuli. Treatment with IFN-\u03b3 results in a rapid and long-lasting suppression of miR-149 in keratinocytes. Depletion of miR-149 in keratinocytes leads to widespread transcriptomic changes and induction of inflammatory mediators with enrichment of the TWEAK pathway. We show that IFN-\u03b3-mediated suppression of miR-149 leads to amplified inflammatory responses to TWEAK. TWEAK receptor (TWEAKR/Fn14) is identified as a novel direct target of miR-149. The in vivo relevance of this pathway is supported by decreased miR-149 expression in psoriasis keratinocytes, as well as by the protective effect of synthetic miR-149 in the imiquimod-induced mouse model of psoriasis.\n\nOur data define a new mechanism, in which IFN-\u03b3 primes keratinocytes for TWEAK-induced inflammatory responses through suppression of miR-149, promoting skin inflammation.", "doi": "10.1016/j.jaci.2020.12.657", "pmid": "33705829", "labels": [], "xrefs": [{"db": "pii", "key": "S0091-6749(21)00361-4"}], "notes": [], "created": "2026-09-23T09:20:36.068Z", "modified": "2026-09-23T09:20:36.105Z"}