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Though treatments arresting disease progression and inducing repigmentation are available, the efficacy of these options is often limited and poorly sustained. How stromal signals contribute to the interferon-\u03b3-dominant skin niches is unclear. This study aims to determine how fibroblasts participate in the IFN-\u03b3-dominant vitiligo niche. Patients and methods: Mouse vitiligo models were established. Fibroblasts from control and vitiligo mice were extracted for RNA sequencing. In vitro IFN-\u03b3 stimulation was performed to verify the JAK-STAT pathway by qPCR and Western blot. T cell polarization with chemokines was measured by flow cytometry. Protein levels in tissues were also examined by IHC. Results: The vitiligo mouse model recapitulates the human CD8-IFN-\u03b3 pathway. RNA sequencing revealed elevated chemokine CCL2 and CCL8 in vitiligo fibroblast, which may be regulated by the JAK-STAT signaling. Such phenomenon is verified by JAK inhibitor peficitinib in vitro. Moreover, CCL2 addition into the na\u00efve T polarization system promoted type 2 cytokines secretion, which represents a hallmark of vitiligo lesions. Conclusion: Dermal fibroblasts, a principal constituent of skin structure, respond to IFN-\u03b3 by skewing T cells towards a type 2 cytokine profile via CCL2 and CCL8, which can be abrogated by JAK inhibitor peficitinib.<\/jats:p>","DOI":"10.3390\/cells12020217","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T01:33:30Z","timestamp":1672882410000},"page":"217","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Pathogenic Th2 Cytokine Profile Skewing by IFN-\u03b3-Responding Vitiligo Fibroblasts via CCL2\/CCL8"],"prefix":"10.3390","volume":"12","author":[{"given":"Rong","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Dermatology, Hangzhou Third People\u2019s Hospital, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaoni","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hangzhou Third People\u2019s Hospital, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5268-4406","authenticated-orcid":false,"given":"Fuquan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hangzhou Third People\u2019s Hospital, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hangzhou Third People\u2019s Hospital, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aie","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hangzhou Third People\u2019s Hospital, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15011","DOI":"10.1038\/nrdp.2015.11","article-title":"Vitiligo","volume":"1","author":"Picardo","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1007\/s13555-020-00447-y","article-title":"Vitiligo, From Physiopathology to Emerging Treatments: A Review","volume":"10","author":"Migayron","year":"2020","journal-title":"Dermatol. Ther. (Heidelb)"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/s41586-021-04221-8","article-title":"Anatomically distinct fibroblast subsets determine skin autoimmune patterns","volume":"601","author":"Xu","year":"2022","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Gegotek, A., Domingues, P., Wronski, A., and Skrzydlewska, E. (2020). Changes in Proteome of Fibroblasts Isolated from Psoriatic Skin Lesions. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155363"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1016\/j.jaci.2013.02.029","article-title":"Role of fibroblasts in the pathogenesis of atopic dermatitis","volume":"131","author":"Berroth","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/j.1600-0749.2006.00326.x","article-title":"In vivo and in vitro evidence of dermal fibroblasts influence on human epidermal pigmentation","volume":"19","author":"Pain","year":"2006","journal-title":"Pigment Cell Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/j.biocel.2010.03.023","article-title":"Signaling pathways in melanosome biogenesis and pathology","volume":"42","author":"Schiaffino","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1111\/exd.13868","article-title":"Involvement of non-melanocytic skin cells in vitiligo","volume":"28","author":"Bastonini","year":"2019","journal-title":"Exp. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/imr.12972","article-title":"Fibroblasts as confederates of the immune system","volume":"302","author":"Jiang","year":"2021","journal-title":"Immunol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"812431","DOI":"10.3389\/fimmu.2022.812431","article-title":"Functional Roles of Chemokine Receptor CCR2 and Its Ligands in Liver Disease","volume":"13","author":"She","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3858","DOI":"10.4049\/jimmunol.1302821","article-title":"CCL2 shapes macrophage polarization by GM-CSF and M-CSF: Identification of CCL2\/CCR2-dependent gene expression profile","volume":"192","author":"Nieto","year":"2014","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.imlet.2003.12.009","article-title":"Impact of tumor-derived CCL2 on T cell effector function","volume":"91","author":"Vitiello","year":"2004","journal-title":"Immunol. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7802","DOI":"10.1038\/ncomms8802","article-title":"Intestinal CD169(+) macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes","volume":"6","author":"Asano","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/ni0211-111","article-title":"CCL8 and skin T cells--an allergic attraction","volume":"12","author":"Debes","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_15","first-page":"S16","article-title":"The role of the Th1 chemokine CXCL10 in vitiligo","volume":"3","author":"Antonelli","year":"2015","journal-title":"Ann. Transl. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.jid.2021.09.015","article-title":"Vitiligo Skin T Cells Are Prone to Produce Type 1 and Type 2 Cytokines to Induce Melanocyte Dysfunction and Epidermal Inflammatory Response Through Jak Signaling","volume":"142","author":"Martins","year":"2022","journal-title":"J. Investig. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"790125","DOI":"10.3389\/fimmu.2021.790125","article-title":"Janus Kinase Inhibitors in the Treatment of Vitiligo: A Review","volume":"12","author":"Qi","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-021-00791-1","article-title":"The JAK\/STAT signaling pathway: From bench to clinic","volume":"6","author":"Hu","year":"2021","journal-title":"Signal. Transduct. Target Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13619-022-00132-9","article-title":"A mouse model of vitiligo based on endogenous auto-reactive CD8 + T cell targeting skin melanocyte","volume":"11","author":"Chen","year":"2022","journal-title":"Cell Regen."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6468","DOI":"10.1158\/0008-5472.CAN-07-1264","article-title":"Induction of postsurgical tumor immunity and T-cell memory by a poorly immunogenic tumor","volume":"67","author":"Zhang","year":"2007","journal-title":"Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1002\/med.21754","article-title":"Mechanisms of melanocyte death in vitiligo","volume":"41","author":"Chen","year":"2021","journal-title":"Med. Res. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.1002\/cpim.63","article-title":"Mouse Model for Human Vitiligo","volume":"124","author":"Riding","year":"2019","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1038\/jid.2009.32","article-title":"Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients","volume":"129","author":"Konijnenberg","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.jid.2017.06.033","article-title":"Vitiligo Skin: Exploring the Dermal Compartment","volume":"138","author":"Kovacs","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1089\/wound.2014.0550","article-title":"The Role of Chemokines in Fibrotic Wound Healing","volume":"4","author":"Ding","year":"2015","journal-title":"Adv. Wound Care (New Rochelle)"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zdanowska, N., Kasprowicz-Furmanczyk, M., Placek, W., and Owczarczyk-Saczonek, A. (2021). The Role of Chemokines in Psoriasis\u2014An Overview. Medicina (Kaunas), 57.","DOI":"10.3390\/medicina57080754"},{"key":"ref_27","first-page":"1798","article-title":"CXCL8 and CXCL11 chemokine secretion in dermal fibroblasts is differentially modulated by vanadium pentoxide","volume":"18","author":"Fallahi","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/35006097","article-title":"Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1","volume":"404","author":"Gu","year":"2000","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/B978-0-12-385071-3.00003-4","article-title":"Targeting chemokine (C-C motif) ligand 2 (CCL2) as an example of translation of cancer molecular biology to the clinic","volume":"95","author":"Zhang","year":"2010","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/ni.1984","article-title":"Mouse CCL8, a CCR8 agonist, promotes atopic dermatitis by recruiting IL-5+ T(H)2 cells","volume":"12","author":"Islam","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev-immunol-100919-023531","article-title":"Vitiligo: Mechanisms of Pathogenesis and Treatment","volume":"38","author":"Frisoli","year":"2020","journal-title":"Annu. Rev. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e262","DOI":"10.1111\/jdv.16240","article-title":"Fibroblasts from atopic dermatitis patients trigger inflammatory processes and hyperproliferation in human skin equivalents","volume":"34","author":"Lowa","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"279","DOI":"10.5021\/ad.2016.28.3.279","article-title":"Skin Pigmentation and Pigmentary Disorders: Focus on Epidermal\/Dermal Cross-Talk","volume":"28","author":"Bastonini","year":"2016","journal-title":"Ann. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.1242\/jcs.064774","article-title":"The fibroblast-derived paracrine factor neuregulin-1 has a novel role in regulating the constitutive color and melanocyte function in human skin","volume":"123","author":"Choi","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/jidsymp.2009.4","article-title":"Regulation of Skin Pigmentation and Thickness by Dickkopf 1 (DKK1)","volume":"14","author":"Yamaguchi","year":"2009","journal-title":"J. Investig. Derm. Symp. P"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"223ra223","DOI":"10.1126\/scitranslmed.3007811","article-title":"CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo","volume":"6","author":"Rashighi","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4049\/jimmunol.1900027","article-title":"The Role of Memory CD8(+) T Cells in Vitiligo","volume":"203","author":"Riding","year":"2019","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/j.0022-202X.2005.23841.x","article-title":"Chemokines: Key players in innate and adaptive immunity","volume":"125","author":"Esche","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5252","DOI":"10.1073\/pnas.88.12.5252","article-title":"Expression of monocyte chemoattractant protein 1 in macrophage-rich areas of human and rabbit atherosclerotic lesions","volume":"88","author":"Lipton","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","first-page":"226","article-title":"Expression of monocyte chemoattractant protein-1 in delayed type hypersensitivity reactions in the skin","volume":"71","author":"Yu","year":"1994","journal-title":"Lab. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1186\/s12935-021-02350-8","article-title":"Correlation of CCL8 expression with immune cell infiltration of skin cutaneous melanoma: Potential as a prognostic indicator and therapeutic pathway","volume":"21","author":"Yang","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1093\/jb\/mvy050","article-title":"CD169 macrophages regulate immune responses toward particulate materials in the circulating fluid","volume":"164","author":"Asano","year":"2018","journal-title":"J. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4602","DOI":"10.4049\/jimmunol.157.10.4602","article-title":"Role of monocyte chemoattractant protein-1 (MCP-1) in Th1 (mycobacterial) and Th2 (schistosomal) antigen-induced granuloma formation: Relationship to local inflammation, Th cell expression, and IL-12 production","volume":"157","author":"Chensue","year":"1996","journal-title":"J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1590\/S1679-45082015RB3438","article-title":"Chemokines and immunity","volume":"13","author":"Palomino","year":"2015","journal-title":"Einstein (Sao Paulo)"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1177\/1203475419833609","article-title":"The Use of Janus Kinase Inhibitors in Vitiligo: A Review of the Literature","volume":"23","author":"Relke","year":"2019","journal-title":"J. Cutan. Med. Surg."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/2\/217\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:58:49Z","timestamp":1760119129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/2\/217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,4]]},"references-count":45,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["cells12020217"],"URL":"https:\/\/doi.org\/10.3390\/cells12020217","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,4]]}}}