{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T06:41:26Z","timestamp":1781851286535,"version":"3.54.5"},"reference-count":38,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Canine pemphigus foliaceus (PF) is considered the most common autoimmune skin disease in dogs; the mechanism of PF disease development is currently poorly understood. Therefore, this study aimed to characterize the molecular mechanisms and altered biological pathways in the skin lesions of canine PF patients. Using an RNA microarray on formalin-fixed, paraffin-embedded samples, we analyzed the transcriptome of canine PF lesional skin (n = 7) compared to healthy skin (n = 5). Of the 800 genes analyzed, 420 differentially expressed genes (DEGs) (p &lt; 0.05) were found. Of those, 338 genes were significantly upregulated, including pro-inflammatory and Th17-related genes. Cell type profiling found enhancement of several cell types, such as neutrophils, T-cells, and macrophages, in PF skin compared to healthy skin. Enrichment analyses of the upregulated DEGs resulted in 78 statistically significant process networks (FDR &lt; 0.05), including the Janus kinase signal transducer and activator of transcription (JAK-STAT) and mitogen-activated protein kinase (MAPK) signaling. In conclusion, canine PF lesional immune signature resembles previously published changes in human pemphigus skin lesions. Further studies with canine PF lesional skin using next-generation sequencing (e.g., RNA sequencing, spatial transcriptomics, etc.) and the development of canine keratinocyte\/skin explant PF models are needed to elucidate the pathogenesis of this debilitating disease.<\/jats:p>","DOI":"10.3390\/vetsci11020089","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T09:30:18Z","timestamp":1707903018000},"page":"89","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Microarray Gene Expression Analysis of Lesional Skin in Canine Pemphigus Foliaceus"],"prefix":"10.3390","volume":"11","author":[{"given":"Haley","family":"Starr","sequence":"first","affiliation":[{"name":"Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth W.","family":"Howerth","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4519-5100","authenticated-orcid":false,"given":"Renato","family":"Leon","sequence":"additional","affiliation":[{"name":"Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3213-4906","authenticated-orcid":false,"suffix":"Jr.","given":"Robert M.","family":"Gogal","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4785-4121","authenticated-orcid":false,"given":"Frane","family":"Banovic","sequence":"additional","affiliation":[{"name":"Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/j.1365-3164.2006.00540.x","article-title":"A review of autoimmune skin diseases in domestic animals: I\u2014Superficial pemphigus","volume":"17","author":"Olivry","year":"2006","journal-title":"Vet. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.jid.2021.04.040","article-title":"Pemphigus and Pemphigoid: From Disease Mechanisms to Druggable Pathways","volume":"142","author":"Ellebrecht","year":"2022","journal-title":"J. Investig. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1016\/j.jaci.2020.11.008","article-title":"Immunophenotyping in pemphigus reveals a T(H)17\/T(FH)17 cell-dominated immune response promoting desmoglein1\/3-specific autoantibody production","volume":"147","author":"Holstein","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"701809","DOI":"10.3389\/fmed.2021.701809","article-title":"Autoantibody-Specific Signalling in Pemphigus","volume":"8","author":"Schmitt","year":"2021","journal-title":"Front. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.3389\/fimmu.2019.02883","article-title":"Role of PKC and ERK Signaling in Epidermal Blistering and Desmosome Regulation in Pemphigus","volume":"10","author":"Egu","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.autrev.2012.10.019","article-title":"p38 mitogen-activated protein kinase (p38 MAPK)-mediated autoimmunity: Lessons to learn from ANCA vasculitis and pemphigus vulgaris","volume":"12","author":"Mavropoulos","year":"2013","journal-title":"Autoimmun. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/j.1365-3164.2010.00924.x","article-title":"Immunomapping of desmosomal and nondesmosomal adhesion molecules in healthy canine footpad, haired skin and buccal mucosal epithelia: Comparison with canine pemphigus foliaceus serum immunoglobulin G staining patterns","volume":"22","author":"Bizikova","year":"2011","journal-title":"Vet. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.vetimm.2012.06.025","article-title":"Cloning and establishment of canine desmocollin-1 as a major autoantigen in canine pemphigus foliaceus","volume":"149","author":"Bizikova","year":"2012","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"110631","DOI":"10.1016\/j.vetimm.2023.110631","article-title":"Characterization of the serum and skin inflammatory profile in canine pemphigus foliaceus using multiplex assay and quantitative real-time polymerase chain reaction (qRT-PCR)","volume":"262","author":"Starr","year":"2023","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_10","unstructured":"Qiu, W., Lee, L.M.-L., and Whitmore, G.A. (2023, September 01). Sample Size and Power Calculation in Microarray Studies Using the Sizepower Package, R Packag Version 132. Available online: https:\/\/bioconductor.org\/packages\/release\/bioc\/vignettes\/sizepower\/inst\/doc\/sizepower.pdf."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Bizikova, P., and Olivry, T. (2015). Oral glucocorticoid pulse therapy for induction of treatment of canine pemphigus foliaceus\u2014A comparative study. Vet. Dermatol., 26.","DOI":"10.1111\/vde.12241"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Chong, E., Austel, M., and Banovic, F. (2022). A Retrospective Evaluation of the Steroid-Sparing Effect of Oral Modified Ciclosporin for Treatment of Canine Pemphigus Foliaceus. Vet. Sci., 9.","DOI":"10.3390\/vetsci9040153"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"77-e24","DOI":"10.1111\/vde.13028","article-title":"A retrospective evaluation of the steroid sparing effects of oral mycophenolate mofetil (MMF) as an adjunct immunosuppressant for the treatment of canine pemphigus foliaceus","volume":"33","author":"Putra","year":"2022","journal-title":"Vet. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Perkins, J.R., Dawes, J.M., McMahon, S.B., Bennett, D.L., Orengo, C., and Kohl, M. (2012). ReadqPCR and NormqPCR: R packages for the reading, quality checking and normalisation of RT-qPCR quantification cycle (Cq) data. BMC Genom., 13.","DOI":"10.1186\/1471-2164-13-296"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"723982","DOI":"10.3389\/fmed.2021.723982","article-title":"Gene Expression Analysis in Four Dogs with Canine Pemphigus Clinical Subtypes Reveals B Cell Signatures and Immune Activation Pathways Similar to Human Disease","volume":"8","author":"Raef","year":"2021","journal-title":"Front. Med."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kowalska-Kepczynska, A., Mleczko, M., Domerecka, W., Krasowska, D., and Donica, H. (2022). Assessment of Immune Cell Activation in Pemphigus. Cells, 11.","DOI":"10.3390\/cells11121912"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1203776","DOI":"10.3389\/fimmu.2023.1203776","article-title":"Skin-infiltrating T cells display distinct inflammatory signatures in lichen planus, bullous pemphigoid and pemphigus vulgaris","volume":"14","author":"Schinner","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_18","first-page":"217","article-title":"Induction of keratinocyte IL-8 expression and secretion by IgG autoantibodies as a novel mechanism of epidermal neutrophil recruitment in a pemphigus variant","volume":"119","author":"Mak","year":"2000","journal-title":"Clin. Exp. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.jaci.2016.08.012","article-title":"Bullous pemphigoid outcome is associated with CXCL10-induced matrix metalloproteinase 9 secretion from monocytes and neutrophils but not lymphocytes","volume":"139","author":"Riani","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jdermsci.2008.09.008","article-title":"Lesional Th17 cells in pemphigus vulgaris and pemphigus foliaceus","volume":"53","author":"Arakawa","year":"2009","journal-title":"J. Dermatol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s12967-022-03387-7","article-title":"Transcriptomic profiling of pemphigus lesion infiltrating mononuclear cells reveals a distinct local immune microenvironment and novel lncRNA regulators","volume":"20","author":"Huang","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ansari, M.A., Singh, P.K., Dar, S.A., Rai, G., Akhter, N., Pandhi, D., Gaurav, V., Bhattacharya, S.N., Banerjee, B.D., and Ahmad, A. (2023). Deregulated phenotype of autoreactive Th17 and Treg clone cells in pemphigus vulgaris after in-vitro treatment with desmoglein antigen (Dsg-3). Immunobiology, 228.","DOI":"10.1016\/j.imbio.2023.152340"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2400","DOI":"10.4049\/jimmunol.1600138","article-title":"IL-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium","volume":"197","author":"Liu","year":"2016","journal-title":"J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8980534","DOI":"10.1155\/2017\/8980534","article-title":"Correlation between IL36alpha and IL17 and Activity of the Disease in Selected Autoimmune Blistering Diseases","volume":"2017","author":"Zebrowska","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"74","DOI":"10.2500\/aap.2015.36.3808","article-title":"Serum interleukin 17, interleukin 23, and interleukin 10 values in children with atopic eczema\/dermatitis syndrome (AEDS): Association with clinical severity and phenotype","volume":"36","author":"Leonardi","year":"2015","journal-title":"Allergy Asthma Proc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.jaad.2010.07.010","article-title":"Expression of the IL-23\/Th17 pathway in lesions of hidradenitis suppurativa","volume":"65","author":"Schlapbach","year":"2011","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s00105-019-4414-8","article-title":"Possible effect of interleukin-17 blockade in pemphigus foliaceus and neutrophilic diseases","volume":"70","author":"Kohlmann","year":"2019","journal-title":"Hautarzt"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.3389\/fimmu.2019.02847","article-title":"Emerging Topical and Systemic JAK Inhibitors in Dermatology","volume":"10","author":"Solimani","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"237-e265","DOI":"10.1111\/vde.13063","article-title":"A case report of the beneficial effect of oclacitinib in a dog with pemphigus vulgaris","volume":"33","author":"Martinez","year":"2022","journal-title":"Vet. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"149-e142","DOI":"10.1111\/vde.13053","article-title":"Prolonged twice-daily administration of oclacitinib for the control of canine atopic dermatitis: A retrospective study of 53 client-owned atopic dogs","volume":"33","author":"Denti","year":"2022","journal-title":"Vet. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/vde.13128","article-title":"Effective treatment of canine chronic cutaneous lupus erythematosus variants with oclacitinib: Seven cases","volume":"34","author":"Harvey","year":"2023","journal-title":"Vet. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/vde.12949","article-title":"Beneficial effect of oclacitinib in a case of feline pemphigus foliaceus","volume":"32","author":"Carrasco","year":"2021","journal-title":"Vet. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.3389\/fimmu.2017.01022","article-title":"Crosstalk between Signaling Pathways in Pemphigus: A Role for Endoplasmic Reticulum Stress in p38 Mitogen-Activated Protein Kinase Activation?","volume":"8","author":"Cipolla","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/s41556-023-01154-4","article-title":"Architecture and dynamics of a desmosome-endoplasmic reticulum complex","volume":"25","author":"Bharathan","year":"2023","journal-title":"Nat. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"iii83","DOI":"10.1136\/ard.2006.058388","article-title":"Mitogen activated protein kinase inhibitors: Where are we now and where are we going?","volume":"65","author":"Sweeney","year":"2006","journal-title":"Ann. Rheum. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"370","DOI":"10.3389\/fimmu.2018.00370","article-title":"Soluble Fas Ligand Is Essential for Blister Formation in Pemphigus","volume":"9","author":"Lotti","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1046\/j.1523-1747.2003.12014.x","article-title":"Fas ligand in pemphigus sera induces keratinocyte apoptosis through the activation of caspase-8","volume":"120","author":"Puviani","year":"2003","journal-title":"J. Investig. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1193032","DOI":"10.3389\/fimmu.2023.1193032","article-title":"Blocking soluble Fas Ligand ameliorates pemphigus: PC111 efficacy in ex-vivo human pemphigus models","volume":"14","author":"Lotti","year":"2023","journal-title":"Front. Immunol."}],"container-title":["Veterinary Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-7381\/11\/2\/89\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:59:34Z","timestamp":1760104774000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-7381\/11\/2\/89"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,14]]},"references-count":38,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["vetsci11020089"],"URL":"https:\/\/doi.org\/10.3390\/vetsci11020089","relation":{},"ISSN":["2306-7381"],"issn-type":[{"value":"2306-7381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,14]]}}}