title: MCPIP1 RNase Is Aberrantly Distributed in Psoriatic Epidermis and Rapidly Induced by IL-17A.
abstract: ZC3H12A, which encodes the RNase monocyte chemotactic protein-induced protein 1 (MCPIP1), is up-regulated in psoriatic skin and reduced to normal levels after clinical treatments with anti-IL-17A/IL-17R neutralizing antibodies. In IL-17A-stimulated keratinocytes, MCPIP1 is rapidly increased at the transcript and protein levels. Also, IL-17A was found to be the main inducer of ZC3H12A expression in keratinocytes treated with supernatants derived from a Streptococcus pyogenes-activated psoriatic ex vivo model based on the co-culture of psoriatic cutaneous lymphocyte-associated antigen (CLA(+)) T cells and lesional epidermal cells. Moreover, MCPIP1 was aberrantly distributed in the suprabasal layers of psoriatic epidermis. In psoriatic samples, IL-17A-stimulated epidermal cell suspensions showed an increased MCPIP1 expression, especially in the mid-differentiated cellular compartment. The knockdown of ZC3H12A showed that this RNase participates in the regulation of the mRNAs present in suprabasal differentiated keratinocytes. Furthermore, JAK/STAT3 inhibition prevented the IL-17A-dependent induction of MCPIP1. In the mouse model of imiquimod-induced psoriasis, Zc3h12a expression was abrogated in Il17ra(-/-) mice. These results support the notion that IL-17A-mediated induction of MCPIP1 is involved in the regulation of local altered gene expression in suprabasal epidermal layers in psoriasis.
authors.affiliation: Translational Immunology, Department of Cellular Biology, Physiology and Immunology, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Ruiz-Romeu
authors.affiliation: Department of Dermatology, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Ferran
authors.affiliation: Department of Dermatology, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Giménez-Arnau
authors.affiliation: Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Bugara
authors.affiliation: Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Lipert
authors.affiliation: Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Jura
authors.affiliation: Department of Dermatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Edwin F
authors.initials: EF
authors.lastname: Florencia
authors.affiliation: Department of Dermatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Errol P
authors.initials: EP
authors.lastname: Prens
authors.affiliation: Macrophage Biology Group, Department of Cellular Biology, Physiology and Immunology, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Celada
authors.affiliation: Department of Dermatology, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Pujol
authors.affiliation: Translational Immunology, Department of Cellular Biology, Physiology and Immunology, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain. Electronic address: luis.santamaria@ub.edu.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Santamaria-Babí
mesh_terms: D000634:Aminoquinolines / Q000737:chemistry; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001706:Biopsy; D018920:Coculture Techniques; D004817:Epidermis / Q000201:enzymology* / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D000077271:Imiquimod; D007249:Inflammation; D020381:Interleukin-17 / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010766:Phosphorylation; D011565:Psoriasis / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D053722:Receptors, Interleukin-17 / Q000378:metabolism; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; D000945:Antigens, Differentiation, T-Lymphocyte; C063419:CTAGE1 protein, human; C109985:IL17RA protein, human; D020381:Interleukin-17; D008562:Membrane Glycoproteins; D053722:Receptors, Interleukin-17; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D012260:Ribonucleases; C510646:ZC3H12A protein, human; C541320:Zc3h12a protein, mouse; D000077271:Imiquimod