Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1371/journal.pone.0145814 http://hdl.handle.net/11449/161076 |
Resumo: | Jorge Lobo's disease (JLD) is a chronic infection that affects the skin and subcutaneous tissues. Its etiologic agent is the fungus Lacazia loboi. Lesions are classified as localized, multifocal, or disseminated, depending on their location. Early diagnosis and the surgical removal of lesions are the best therapeutic options currently available for JLD. The few studies that evaluate the immunological response of JLD patients show a predominance of Th2 response, as well as a high frequency of TGF-beta and IL-10 positive cells in the lesions; however, the overall immunological status of the lesions in terms of their T cell phenotype has yet to be determined. Therefore, the objective of this study was to evaluate the pattern of Th1, Th2, Th17 and regulatory T cell (Treg) markers mRNA in JLD patients by means of real-time PCR. Biopsies of JLD lesions (N = 102) were classified according to their clinical and histopathological features and then analyzed using real-time PCR in order to determine the expression levels of TGF-beta 1, FoxP3, CTLA4, IKZF2, IL-10, T-bet, IFN-gamma, GATA3, IL-4, IL-5, IL-13, IL-33, RORC, IL-17A, IL-17F, and IL-22 and to compare these levels to those of healthy control skin (N = 12). The results showed an increased expression of FoxP3, CTLA4, TGF-beta 1, IL-10, T-bet, IL-17F, and IL-17A in lesions, while GATA3 and IL-4 levels were found to be lower in diseased skin than in the control group. When the clinical forms were compared, TGF-beta 1 was found to be highly expressed in patients with a single localized lesion while IL-5 and IL-17A levels were higher in patients with multiple/disseminated lesions. These results demonstrate the occurrence of mixed T helper responses and suggest the dominance of regulatory T cell activity, which could inhibit Th-dependent protective responses to intracellular fungi such as L. loboi. Therefore, Tregs may play a key role in JLD pathogenesis. |
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Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell ActivityJorge Lobo's disease (JLD) is a chronic infection that affects the skin and subcutaneous tissues. Its etiologic agent is the fungus Lacazia loboi. Lesions are classified as localized, multifocal, or disseminated, depending on their location. Early diagnosis and the surgical removal of lesions are the best therapeutic options currently available for JLD. The few studies that evaluate the immunological response of JLD patients show a predominance of Th2 response, as well as a high frequency of TGF-beta and IL-10 positive cells in the lesions; however, the overall immunological status of the lesions in terms of their T cell phenotype has yet to be determined. Therefore, the objective of this study was to evaluate the pattern of Th1, Th2, Th17 and regulatory T cell (Treg) markers mRNA in JLD patients by means of real-time PCR. Biopsies of JLD lesions (N = 102) were classified according to their clinical and histopathological features and then analyzed using real-time PCR in order to determine the expression levels of TGF-beta 1, FoxP3, CTLA4, IKZF2, IL-10, T-bet, IFN-gamma, GATA3, IL-4, IL-5, IL-13, IL-33, RORC, IL-17A, IL-17F, and IL-22 and to compare these levels to those of healthy control skin (N = 12). The results showed an increased expression of FoxP3, CTLA4, TGF-beta 1, IL-10, T-bet, IL-17F, and IL-17A in lesions, while GATA3 and IL-4 levels were found to be lower in diseased skin than in the control group. When the clinical forms were compared, TGF-beta 1 was found to be highly expressed in patients with a single localized lesion while IL-5 and IL-17A levels were higher in patients with multiple/disseminated lesions. These results demonstrate the occurrence of mixed T helper responses and suggest the dominance of regulatory T cell activity, which could inhibit Th-dependent protective responses to intracellular fungi such as L. loboi. Therefore, Tregs may play a key role in JLD pathogenesis.Univ Estadual Paulista, Fac Med Botucatu, Dept Doencas Trop, Botucatu, SP, BrazilInst Lauro Souza Lima, Dept Patol, Sao Paulo, BrazilInst Lauro Souza Lima, Dept Microbiol, Sao Paulo, BrazilHosp Clin Acre, Serv Especializado Dermatol, Sao Paulo, BrazilUniv Sao Paulo, Fac Odontol Bauru, Dept Ciencias Biol, Sao Paulo, BrazilUniv Sagrado Coracao, Dept Ciencias Saude, Sao Paulo, BrazilUniv Estadual Paulista, Fac Med Botucatu, Dept Doencas Trop, Botucatu, SP, BrazilPublic Library ScienceUniversidade Estadual Paulista (Unesp)Inst Lauro Souza LimaHosp Clin AcreUniversidade de São Paulo (USP)Univ Sagrado CoracaoAzevedo, Michelle de C. S. [UNESP]Rosa, Patricia S.Soares, Cleverson T.Fachin, Luciana R. V.Baptista, Ida Maria F. D.Woods, William J.Garlet, Gustavo P.Trombone, Ana Paula F.Belone, Andrea de F. F.2018-11-26T16:19:02Z2018-11-26T16:19:02Z2015-12-23info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article17application/pdfhttp://dx.doi.org/10.1371/journal.pone.0145814Plos One. San Francisco: Public Library Science, v. 10, n. 12, 17 p., 2015.1932-6203http://hdl.handle.net/11449/16107610.1371/journal.pone.0145814WOS:000367092600135WOS000367092600135.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPlos One1,164info:eu-repo/semantics/openAccess2024-08-15T15:23:14Zoai:repositorio.unesp.br:11449/161076Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-15T15:23:14Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity |
title |
Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity |
spellingShingle |
Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity Azevedo, Michelle de C. S. [UNESP] |
title_short |
Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity |
title_full |
Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity |
title_fullStr |
Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity |
title_full_unstemmed |
Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity |
title_sort |
Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity |
author |
Azevedo, Michelle de C. S. [UNESP] |
author_facet |
Azevedo, Michelle de C. S. [UNESP] Rosa, Patricia S. Soares, Cleverson T. Fachin, Luciana R. V. Baptista, Ida Maria F. D. Woods, William J. Garlet, Gustavo P. Trombone, Ana Paula F. Belone, Andrea de F. F. |
author_role |
author |
author2 |
Rosa, Patricia S. Soares, Cleverson T. Fachin, Luciana R. V. Baptista, Ida Maria F. D. Woods, William J. Garlet, Gustavo P. Trombone, Ana Paula F. Belone, Andrea de F. F. |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Inst Lauro Souza Lima Hosp Clin Acre Universidade de São Paulo (USP) Univ Sagrado Coracao |
dc.contributor.author.fl_str_mv |
Azevedo, Michelle de C. S. [UNESP] Rosa, Patricia S. Soares, Cleverson T. Fachin, Luciana R. V. Baptista, Ida Maria F. D. Woods, William J. Garlet, Gustavo P. Trombone, Ana Paula F. Belone, Andrea de F. F. |
description |
Jorge Lobo's disease (JLD) is a chronic infection that affects the skin and subcutaneous tissues. Its etiologic agent is the fungus Lacazia loboi. Lesions are classified as localized, multifocal, or disseminated, depending on their location. Early diagnosis and the surgical removal of lesions are the best therapeutic options currently available for JLD. The few studies that evaluate the immunological response of JLD patients show a predominance of Th2 response, as well as a high frequency of TGF-beta and IL-10 positive cells in the lesions; however, the overall immunological status of the lesions in terms of their T cell phenotype has yet to be determined. Therefore, the objective of this study was to evaluate the pattern of Th1, Th2, Th17 and regulatory T cell (Treg) markers mRNA in JLD patients by means of real-time PCR. Biopsies of JLD lesions (N = 102) were classified according to their clinical and histopathological features and then analyzed using real-time PCR in order to determine the expression levels of TGF-beta 1, FoxP3, CTLA4, IKZF2, IL-10, T-bet, IFN-gamma, GATA3, IL-4, IL-5, IL-13, IL-33, RORC, IL-17A, IL-17F, and IL-22 and to compare these levels to those of healthy control skin (N = 12). The results showed an increased expression of FoxP3, CTLA4, TGF-beta 1, IL-10, T-bet, IL-17F, and IL-17A in lesions, while GATA3 and IL-4 levels were found to be lower in diseased skin than in the control group. When the clinical forms were compared, TGF-beta 1 was found to be highly expressed in patients with a single localized lesion while IL-5 and IL-17A levels were higher in patients with multiple/disseminated lesions. These results demonstrate the occurrence of mixed T helper responses and suggest the dominance of regulatory T cell activity, which could inhibit Th-dependent protective responses to intracellular fungi such as L. loboi. Therefore, Tregs may play a key role in JLD pathogenesis. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-12-23 2018-11-26T16:19:02Z 2018-11-26T16:19:02Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1371/journal.pone.0145814 Plos One. San Francisco: Public Library Science, v. 10, n. 12, 17 p., 2015. 1932-6203 http://hdl.handle.net/11449/161076 10.1371/journal.pone.0145814 WOS:000367092600135 WOS000367092600135.pdf |
url |
http://dx.doi.org/10.1371/journal.pone.0145814 http://hdl.handle.net/11449/161076 |
identifier_str_mv |
Plos One. San Francisco: Public Library Science, v. 10, n. 12, 17 p., 2015. 1932-6203 10.1371/journal.pone.0145814 WOS:000367092600135 WOS000367092600135.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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Plos One 1,164 |
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info:eu-repo/semantics/openAccess |
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openAccess |
dc.format.none.fl_str_mv |
17 application/pdf |
dc.publisher.none.fl_str_mv |
Public Library Science |
publisher.none.fl_str_mv |
Public Library Science |
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Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
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Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
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UNESP |
reponame_str |
Repositório Institucional da UNESP |
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Repositório Institucional da UNESP |
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Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
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1808128180056227840 |