039 Early onset pediatric atopic dermatitis skin phenotype is Th2, but also Th17-polarized

Abstract

Bullous pemphigoid (BP) is an autoimmune blistering skin disease caused by autoantibody against the hemidesmosomal protein BP180. B regulatory cells (Bregs) are crucial in maintaining self-tolerance and suppressing autoantibody production. Blood samples were collected from thirty-six BP patients and thirty healthy volunteers. The number of CD19 + CD24 hi CD27 + Bregs was analyzed by flow cytometry. Elisa assay was performed to detect the level of anti-BP180 autoantibodies produced by patient-derived peripheral blood mononuclear cells (PBMCs) with Bregs deletion or without. In addition, T cells were cultured with autogenous Bregs from BP patients or healthy controls respectively, then the proliferation and cytokine productions in these T cells were detected by flow cytometry. Finally, the expressions of IL-10 and TNF-a in Bregs were further examined. Then etanercept was added into the culture of patients-derived PBMCs to investigate the role of TNF-a in autoantibody production. The frequency of circulating CD19 + CD24 hi CD27 + Bregs increased in BP patients compared with healthy controls. However, patient-derived Bregs were impaired in suppressing the production of specific anti-BP180 autoantibodies. These patients-derived Bregs were also defective in suppressing CD4 + T cell activation. Further, patient-derived Bregs produced comparable level of IL-10, while aberrantly secreted TNF-a. Etanercept could inhibit the autoantibody production in patient-derived PBMCs. Our results suggested that BP patient-derived Bregs were impaired in suppressing CD4 + T cell activation in a manner of aberrant secretion of TNF-a, rather than IL-10, thus contributing to the autoantibody production.

The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies

“…113 Remarkable differences also have been detected in a recent study between the skin profiles of infants and adults. 114 While both early-onset pediatric as well as adult AD show a strong Th2 activation, there is increased innate and IL-17-related inflammation in early AD lesions of infants. This dual upregulation of both Th2 and Th17 responses might be explained by profoundly increased levels of IL-19, a cytokine that can be induced by both IL-17 and IL-4/IL-13, and which has been shown to amplify the effects of IL-17 on keratinocytes.…”

“…This dual upregulation of both Th2 and Th17 responses might be explained by profoundly increased levels of IL-19, a cytokine that can be induced by both IL-17 and IL-4/IL-13, and which has been shown to amplify the effects of IL-17 on keratinocytes. 115 Besides Th17 responses, early-onset pediatric AD showed increased levels of antimicrobial peptides (AMP), 114 comparable to levels in adult psoriasis. This increase in AMP might serve as a danger signal triggering disease, as demonstrated in psoriasis, where complexes of AMP with either self-DNA or RNA can stimulate dendritic cell activation.…”

“…This increase in AMP might serve as a danger signal triggering disease, as demonstrated in psoriasis, where complexes of AMP with either self-DNA or RNA can stimulate dendritic cell activation. 116,117 However, control skin from healthy infants also showed elevated levels of Th17 and Th22 associated mediators, including AMPs, 114,118,119 possibly rooted in the necessity of newborn skin to combat infections when the skin immune system is not yet fully developed. Thus, the pathogenic role of these immune axes in children need to ultimately be evaluated through clinical trials.…”

“…Strikingly, the filaggrin deficiency of adult AD was missing in early AD, 114 perhaps challenging the notion of defective filaggrin as primary factor for disease elicitation and an instigator of the atopic march. Future studies will need to further characterize epidermal barrier features in early-onset AD.…”

“…114 Thus, the non-lesional skin of children with early AD can be viewed as a true state of disease initiation. Interestingly, at 2 months of age prior to onset of AD, infant non-lesional skin contain increased TSLP, a cytokine that drives differentiation of Th2 cells.…”