Case Series: Gene Expression Analysis in Canine Vogt-Koyanagi-Harada/Uveodermatologic Syndrome and Vitiligo Reveals Conserved Immunopathogenesis Pathways Between Dog and Human Autoimmune Pigmentary Disorders

Egbeto, Ista A.; Garelli, Colton J.; Piedra-Mora, César; Wong, Neil B.; David, Clément N.; Robinson, Nicholas A.; Richmond, Julius B.

doi:10.3389/fimmu.2020.590558

Cited by 15 publications

(7 citation statements)

References 83 publications

(87 reference statements)

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“…One study indicated that rs4946936 of the FOXO3A gene might be associated with susceptibility to vitiligo, especially active vitiligo, and FOXO3A levels were decreased in vitiligo patients compared with normal controls [ 17 ]. Another study reported the downregulation of FOXO1 in vitiligo lesional skin [ 18 ]. Integrins are proteins that link the cell cytoskeleton to the extracellular matrix (ECM) mechanically and biochemically.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Autophagy-Related Genes in Vitiligo

Yang

et al. 2022

Cells

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Vitiligo is a common depigmented disease with unclear pathogenesis. Autophagy is crucial for maintaining cellular homeostasis and has been linked to a variety of autoimmune disorders; however, there have been no reports exploring the involvement of autophagy-related genes (ARGs) in vitiligo using bioinformatics methodologies. In this study, RNA-sequencing technology was used to identify the differentially expressed genes (DEGs) and the Human Autophagy Database (HADb) was overlapped to identify differentially expressed autophagy-related genes (DEARGs) in stable non-segmental vitiligo (NSV). Bioinformatics analyses were conducted with R packages and Ingenuity Pathways Analysis (IPA). DEARGs were further confirmed with qRT-PCR. Critical autophagy markers were detected with Western blotting analysis. We identified a total of 39 DEARGs in vitiligo lesions. DEARGs-enriched canonical pathways, diseases and bio functions, upstream regulators, and networks were discovered. qRT-PCR confirmed the significant increases in FOS and RGS19 in vitiligo lesions. Lower microtubule-associated protein 1 light chain (LC3) II/LC3I ratio and higher sequestosome 1 (SQSTM1, p62) expression were found in vitiligo lesions. In conclusion, this study provided a new insight that autophagy dysregulation appeared in stable vitiligo lesions and might be involved in the etiology of vitiligo by taking part in multiple pathways and bio functions.

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Section: Discussionmentioning

confidence: 99%

Identification and Validation of Autophagy-Related Genes in Vitiligo

Yang

et al. 2022

Cells

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“…Moreover, many other factors, including intestinal flora, viral infection, and genetic factors, are involved. 3 Among these factors, the intestinal flora has received increasing attention. It has been recognized that intestinal flora is related to some autoimmune diseases, such as Behcet disease, rheumatoid arthritis, and inflammatory bowel disease.…”

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confidence: 99%

Enriched and Decreased Intestinal Microbes in Active VKH Patients

Yang

Cao

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose To determine the possible microbiome related to Vogt–Koyanagi–Harada (VKH) disease in comparison to patients with noninfectious anterior scleritis and healthy people. Methods Fecal samples were extracted from 42 individuals, including 11 patients with active VKH, 11 healthy people, and 20 patients with noninfectious anterior scleritis. We amplified the V3 to V4 16S ribosomal DNA (rDNA) region to obtain the target sequence. Then, the target sequence was amplified by polymerase chain reaction. The obtained target sequences were sequenced by high-throughput 16S rDNA analysis. Results At the genus level, there were three enriched ( Stomatobaculum , Pseudomonas , Lachnoanaerobaculum ) and two depleted ( Gordonibacter , Slackia ) microbes that were detected only in patients with VKH. There were 10 enriched and 12 depleted microbes that were observed in both patients with VKH disease and noninfectious anterior scleritis ( P < 0.05). The interactions of these microbes were graphed. Tyzzerella and Eggerthella were the nodes of interaction between these microorganisms, which were regulated by both positive and negative aspects, but the expression level in patients with active VKH was upregulated. Conclusions Special or nonspecial enrichment and decreased intestinal microbes were observed in patients with active VKH. The action mechanism of these microbes needs further study.

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“…Specifically, as in active SLV, the loss of choroidal melanocytes is associated with an INF-γ polarized, Th1 cell-mediated immune response and aberrant melanocyte function. The immunopathogenesis in SL vision impairment resembles induced uveitis and human ocular diseases, especially Vogt–Koyanagi–Harada syndrome and sympathetic ophthalmia, both of which are autoimmune disorders associated with vitiligo ( 7 , 32 – 34 ). Hence, the Smyth chicken model provides the opportunity to expand our understanding of spontaneous autoimmune pigmentation disorders, including autoimmune pigmentation loss associated with melanoma therapy ( 35 ), and develop effective treatment and prevention strategies.…”

Section: Discussionmentioning

confidence: 99%

Immune Activities in Choroids of Visually Impaired Smyth Chickens With Autoimmune Vitiligo

et al. 2022

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Vitiligo is a common dermatological disorder affecting 1–2% of the world’s population. It is characterized by postnatal, autoimmune destructions of melanocytes in the skin, resulting in patches of depigmentation. Autoimmunity in vitiligo may also affect melanocytes in non-integumental tissues, including the eyes where choroidal melanocytes are the target of the autoimmune response. The Smyth line (SL) of chicken is the only animal model that spontaneously and predictably develops all clinical and biological manifestations of autoimmune vitiligo. In SL vitiligo (SLV), destruction of epidermal melanocytes in growing feathers (GFs) involves a melanocyte-specific, Th1-mediated cellular immune response. Smyth chickens may also exhibit uveitis and vision impairment. Previous studies established a strong association between SLV and vision impairment, including similar pathology in affected eyes and GFs. To determine the presence, types, and activities of choroid infiltrating mononuclear cells, we collected eyes before, near onset, and during active SLV from sighted, partially blind, and blind SL chickens. All SL chickens with vision impairment had SLV. Immunohistochemistry and quantitative reverse transcriptase-PCR analyses revealed mononuclear cell and cytokine expression profiles in the autoimmune destruction of melanocytes in choroids that are identical to those described in GF, demonstrating the systemic nature of autoimmunity against melanocytes in SLV. In addition, we observed aberrant melanogenesis in SL eyes. The immunopathogenesis in SL vision impairment resembles human vitiligo-associated ocular diseases, especially Vogt–Koyanagi–Harada syndrome and sympathetic ophthalmia. Hence, the Smyth chicken autoimmune vitiligo model provides the opportunity to expand our understanding of spontaneous autoimmune pigmentation disorders and to develop effective treatment strategies.

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Case Series: Gene Expression Analysis in Canine Vogt-Koyanagi-Harada/Uveodermatologic Syndrome and Vitiligo Reveals Conserved Immunopathogenesis Pathways Between Dog and Human Autoimmune Pigmentary Disorders

Cited by 15 publications

References 83 publications

Identification and Validation of Autophagy-Related Genes in Vitiligo

Identification and Validation of Autophagy-Related Genes in Vitiligo

Enriched and Decreased Intestinal Microbes in Active VKH Patients

Immune Activities in Choroids of Visually Impaired Smyth Chickens With Autoimmune Vitiligo

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