Mandron Marie, Ariès Marie-Françoise, Boralevi Franck, Martin Hélène, Charveron Marie, Taieb Alain, Davrinche Christian
INSERM, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
J Invest Dermatol. 2008 Apr;128(4):882-9. doi: 10.1038/sj.jid.5701112. Epub 2007 Oct 25.
As shown by atopy patch tests, atopic dermatitis (AD) is dominated in its acute phase by the development of a specific T(H)2 response after exposure of the skin to common environmental antigens. Relying on our previous data showing that Staphylococcus aureus enterotoxin B (SEB) induced the activation of monocyte-derived dendritic cells (DCs) through Toll-like receptor (TLR)2 and that SEB-pulsed DCs commit allogenic naive T cells into T(H)2, we assessed monocytes sensitivity to SEB and lipopolysaccharide (LPS) in a group of children and adult patients with AD. Monocytes from AD patients (15 adults with mostly severe disease and 15 children with mild to moderate disease) exhibited an activated and tolerant state as supported by (i) secretion of large amounts of IL-6, IL-10, and tumor necrosis factor-alpha even in the absence of stimulation; (ii) their inability to modulate neither HLA-DR and CD54 nor TLR2 and TLR4 expression after in vitro challenge with SEB; (iii) inhibition of IL-12p70 secretion in response to LPS. Interestingly, monocytes from some of the children studied responded to in vitro challenge with LPS, suggesting new hypotheses to explain disease regression. Our data support the notion that monitoring sensitivity of monocytes to bacterial toxins could prove useful to assess disease progression and prognosis in AD.
如特应性皮炎斑贴试验所示,在急性期,特应性皮炎(AD)主要表现为皮肤暴露于常见环境抗原后出现特异性T(H)2反应。基于我们之前的数据,即金黄色葡萄球菌肠毒素B(SEB)通过Toll样受体(TLR)2诱导单核细胞衍生的树突状细胞(DCs)活化,且经SEB刺激的DCs可使同种异体幼稚T细胞分化为T(H)2细胞,我们评估了一组儿童和成人AD患者的单核细胞对SEB和脂多糖(LPS)的敏感性。AD患者(15名大多患有严重疾病的成人和15名患有轻至中度疾病的儿童)的单核细胞表现出活化和耐受状态,表现为:(i)即使在无刺激情况下也分泌大量白细胞介素-6、白细胞介素-10和肿瘤坏死因子-α;(ii)经SEB体外刺激后,它们无法调节HLA-DR和CD54以及TLR2和TLR4的表达;(iii)对LPS刺激的反应中白细胞介素-12p70分泌受到抑制。有趣的是,部分受试儿童的单核细胞对LPS体外刺激有反应,这为解释疾病消退提出了新的假说。我们的数据支持这样一种观点,即监测单核细胞对细菌毒素的敏感性可能有助于评估AD的疾病进展和预后。