The dysfunctional innate immune response triggered by Toll-like receptor activation is restored by TLR7/TLR8 and TLR9 ligands in cutaneous lichen planus

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art_DOMINGUES_The_dysfunctional_innate_immune_response_triggered_by_Tolllike_2015.PDF (468.29 KB)
Citações na Scopus
18
Tipo de produção
article
Data de publicação
2015
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
WILEY-BLACKWELL
Autores
TANIGUCHI, E. Futata
Citação
BRITISH JOURNAL OF DERMATOLOGY, v.172, n.1, p.48-55, 2015
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
BackgroundLichen planus (LP) is a chronic inflammatory mucocutaneous disease. Toll-like receptors (TLRs) bind numerous exogenous and endogenous antigens by recognizing conserved pathogen-associated molecular patterns (PAMPs) and have the ability to induce the production of proinflammatory cytokines. Therefore, alterations in innate immunity could explain the inflammation and T-cell autoreactivity leading to the development of LP disease. ObjectivesTo evaluate how the host innate immune response to PAMPs is affected by cutaneous LP, primarily by using TLR agonists to induce proinflammatory cytokine secretion from peripheral blood mononuclear cells (PBMCs). MethodsPBMCs from patients with LP and healthy control (HC) individuals were stimulated with agonists of TLR2/TLR1 (pam3csk4), TLR3 [poly(I:C)-RIG], TLR4 (lipopolysaccharide), TLR5 (flagellin), TLR7 (imiquimod), TLR7/TLR8 (CL097) and TLR9 (CpG). Cytokines from culture supernatants (n=10-12) andserum chemokines and cytokines (n=22-24) were measured using flow cytometry. ResultsActivation through the TLR2, TLR4 and TLR5 pathways induced increased tumour necrosis factor (TNF)- secretion by PBMCs from individuals with LP compared with the HC group. In contrast, activation through TLR3 and TLR7 was impaired in the LP group, leading to decreased TNF- secretion. Moreover, intracellular TLR activation resulted in reduced interleukin (IL)-1 and IL-6 secretion. Notably, individuals with LP became responders on stimulation with TLR7/TLR8 and TLR9 agonists; responses were measured as increases in interferon (IFN)- production. Detectable TNF- and high CXCL9 and CXCL10 serum levels were observed in patients with LP, suggesting their potential use as markers of the inflammatory status in LP. ConclusionsThese findings point to a defect in the TLR signalling pathways in cutaneous LP. Agonists of TLR7/TLR8 or TLR9 overcame impaired IFN- secretion in LP, strategically acting as adjuvants to improve the type I response.
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URI
https://observatorio.fm.usp.br/handle/OPI/9341
Referências
  1. Abdulahad DA, 2013, LUPUS, V22, P597, DOI 10.1177/0961203313483377
  2. Antonelli A, 2014, AUTOIMMUN REV, V13, P272, DOI 10.1016/j.autrev.2013.10.010
  3. Borkowski AW, 2014, J INVEST DERMATOL, V134, P2315, DOI 10.1038/jid.2014.167
  4. BOYD AS, 1991, J AM ACAD DERMATOL, V25, P593, DOI 10.1016/0190-9622(91)70241-S
  5. Cardoso EC, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0067036
  6. Casrouge A, 2012, CLIN EXP IMMUNOL, V167, P137, DOI 10.1111/j.1365-2249.2011.04488.x
  7. Cella M, 1999, NAT MED, V5, P919
  8. Chan JK, 2012, J CLIN INVEST, V122, P2711, DOI 10.1172/JCI62423
  9. Church LD, 2008, NAT CLIN PRACT RHEUM, V4, P34, DOI 10.1038/ncprheum0681
  10. De Vries HJC, 2006, BRIT J DERMATOL, V154, P361, DOI 10.1111/j.1365-2133.2005.06999.x
  11. El Tawdy A, 2012, INT J DERMATOL, V51, P785, DOI 10.1111/j.1365-4632.2011.04977.x
  12. Erdem MT, 2003, DERMATOLOGY, V207, P367, DOI 10.1159/000074116
  13. Garcia-Lopez MA, 2001, LAB INVEST, V81, P409
  14. Gilliet M, 2008, NAT REV IMMUNOL, V8, P594, DOI 10.1038/nri2358
  15. Huang WJ, 2012, J IMMUNOL, V188, P6247, DOI 10.4049/jimmunol.1103706
  16. Iijima W, 2003, AM J PATHOL, V163, P261, DOI 10.1016/S0002-9440(10)63649-8
  17. IRVINE C, 1991, ACTA DERM-VENEREOL, V71, P242
  18. Janardhanam SB, 2012, ARCH ORAL BIOL, V57, P495, DOI 10.1016/j.archoralbio.2011.10.013
  19. Jin X, 2012, J DERMATOL SCI, V68, P127, DOI 10.1016/j.jdermsci.2012.09.003
  20. Kaczanowska S, 2013, J LEUKOCYTE BIOL, V93, P847, DOI 10.1189/jlb.1012501
  21. KARAGOUNI EE, 1994, J ORAL PATHOL MED, V23, P28, DOI 10.1111/j.1600-0714.1994.tb00250.x
  22. Kawai T, 2010, NAT IMMUNOL, V11, P373, DOI 10.1038/ni.1863
  23. Lemon SM, 2010, J BIOL CHEM, V285, P22739, DOI 10.1074/jbc.R109.099556
  24. Lodi G, 2004, BRIT J DERMATOL, V151, P1172, DOI 10.1111/j.1365-2133.2004.06257.x
  25. Netea MG, 2003, TRENDS IMMUNOL, V24, P254, DOI 10.1016/S1471-4906(03)00079-6
  26. Pekiner FN, 2012, CYTOKINE, V60, P701, DOI 10.1016/j.cyto.2012.08.007
  27. Raman VS, 2010, J IMMUNOL, V185, P1701, DOI 10.4049/jimmunol.1000238
  28. Rehermann B, 2009, J CLIN INVEST, V119, P1745, DOI 10.1172/JCI39133
  29. Salem SAM, 2013, ARCH DERMATOL RES, V305, P125, DOI 10.1007/s00403-012-1267-8
  30. SanchezPerez J, 1996, BRIT J DERMATOL, V134, P715, DOI 10.1111/j.1365-2133.1996.tb06977.x
  31. Schoenemeyer A, 2005, J BIOL CHEM, V280, P17005, DOI 10.1074/jbc.M412584200
  32. Schroder K, 2010, CELL, V140, P821, DOI 10.1016/j.cell.2010.01.040
  33. Siponen M, 2012, J ORAL PATHOL MED, V41, P741, DOI 10.1111/j.1600-0714.2012.01169.x
  34. Stanimirovic D, 2013, EUR J ORAL SCI, V121, P421, DOI 10.1111/eos.12074
  35. YAMAMOTO T, 1991, J ORAL PATHOL MED, V20, P275, DOI 10.1111/j.1600-0714.1991.tb00927.x
  36. Zunt SL, 2009, CLIN EXP IMMUNOL, V156, P285, DOI 10.1111/j.1365-2249.2009.03854.x

Coleções
Artigos e Materiais de Revistas Científicas - FM/MDT
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/56