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Rôle de Fc epsilon RI, CD16 et PPAR-alpha dans la dermatite atopique

Abstract : Atopic dermatitis (AD) is a common chronic inflammatory skin disease caracterized by increased epidermal thickness and a dermal infiltration with activated memory T cells, macrophages, mast cells and eosinophils as well as Th2- and Th1- associated cytokine profiles in acute and chronic skin lesions respectively. Most AD patients show elevated total and allergen- or microbe-specific IgE and IgG levels in serum. The high and low affinity IgE receptors, FcepsilonRI and FcepsilonRII/CD23, and the low affinity IgG receptor, FcgammaRIII/CD16 play an essential role in allergic diseases. In human skin, those FcR are expressed by antigen presenting cells and effector cells resident or recruited into the inflamed dermis. In this work, we have studied the role of those receptors in a mouse model of AD that mimics the human pathology by comparing FcR-deficient animals with their corresponding WT counterparts. Symptoms of AD are completely absent in FcRgamma-deficient animals but only partially inhibited in either FcepsilonRI- or FcgammaRIII/CD16-deficient animals. This inhibition is correlated with increased skin expression of regulatory IL-10 and Foxp3. While FcepsilonRI controls both Th1 and Th2 skin response, mast cell recruitment into draining lymh nodes and IgE production, CD16 regulates only Th2 skin response, as well as T cell proliferation and IgG1 production. This isotype-specific regulation by the cognate FcR is associated to a differential regulation of IL-4 and IL-21 expression in the draining lymph nodes. Importantly, CD23 deficiency also led to a drastic inhibition of the pathology and, like FcepsilonRI, to decreased Th1 and Th2 skin responses and IgE but not IgG1 production. We also investigated the regulatory role of the nuclear receptor PPAR-alpha in this AD model. Indeed, it is expressed in several cells of the immune system and have anti-inflammatory activities in other pathologies. Upon antigen sensitization, we found that PPAR-alpha–deficient mice display increased skin and lung responses as well as IgE and IgG2a production compared with their wild-type counterparts. This phenomenon is correlated with an enhancement of Th2 and, to a greater extent, Th1 responses as well as an increased skin expression of nuclear factor-kappaB. Interestingly, PPAR-alpha expression was decreased in eczematous skin from patients with AD compared with skin from nonatopic donors, suggesting that defective PPAR-alpha expression might contribute to the pathology. Topical application of WY14.643, a specific PPAR-alpha agonist, significantly decreased antigen-induced skin inflammation in the AD model. Thus, we have delineated the contribution of IgE/FcepsilonR and IgG/FcgammaR to AD pathophysiology. Finally, targeting interactions between IgE and its 2 FcepsilonR, IgG and FcgammaR as well as PPAR-alpha represent efficient therapeutic strategies for allergic diseases.
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Contributor : Georges Abboud <>
Submitted on : Wednesday, June 4, 2008 - 11:35:30 AM
Last modification on : Thursday, February 21, 2019 - 9:56:02 AM
Long-term archiving on: : Friday, November 25, 2016 - 9:17:45 PM


  • HAL Id : tel-00285004, version 1



Georges Abboud. Rôle de Fc epsilon RI, CD16 et PPAR-alpha dans la dermatite atopique. Immunologie. Université du Droit et de la Santé - Lille II, 2008. Français. ⟨tel-00285004⟩



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