The dysfunctional innate immune response triggered by Toll-like receptor activation is restored by TLR7/TLR8 and TLR9 ligands in cutaneous lichen planus.
Br J Dermatol
; 172(1): 48-55, 2015 Jan.
Article
en En
| MEDLINE
| ID: mdl-24976336
ABSTRACT
BACKGROUND:
Lichen 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.OBJECTIVES:
To 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).METHODS:
PBMCs from patients with LP and healthy control (HC) individuals were stimulated with agonists of TLR2/TLR1 (pam3csk4), TLR3 [poly(IC)-RIG], TLR4 (lipopolysaccharide), TLR5 (flagellin), TLR7 (imiquimod), TLR7/TLR8 (CL097) and TLR9 (CpG). Cytokines from culture supernatants (n = 10-12) and serum chemokines and cytokines (n = 22-24) were measured using flow cytometry.RESULTS:
Activation through the TLR2, TLR4 and TLR5 pathways induced increased tumour necrosis factor (TNF)-α 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-α secretion. Moreover, intracellular TLR activation resulted in reduced interleukin (IL)-1ß 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)-α production. Detectable TNF-α 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.CONCLUSIONS:
These findings point to a defect in the TLR signalling pathways in cutaneous LP. Agonists of TLR7/TLR8 or TLR9 overcame impaired IFN-α secretion in LP, strategically acting as adjuvants to improve the type I response.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Receptores Toll-Like
/
Inmunidad Innata
/
Liquen Plano
Límite:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Br J Dermatol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Brasil