Absence of the adaptor protein Shb potentiates the T helper type 2 response in a mouse model of atopic dermatitis. Issue 1 (September 2014)

• Record Type: Journal Article
• Authors: Gustafsson, Karin; Willebrand, Elsa; Welsh, Michael
• Is Part Of: Immunology. Volume 143:Issue 1(2014:Sep.)
• Page Start: 33
• Page End: 41
• Publication Date: 2014-09
• Subjects: Immunology -- Periodicals
• DOI: 10.1111/imm.12286
• Languages: English
• ISSNs: 0019-2805

Abstract

<abstract abstract-type="main" id="imm12286-abs-0001"> <title>Summary</title> <p>Aberrant regulation of T helper (Th) cell maturation is associated with a number of autoimmune conditions, including allergic disorders and rheumatoid arthritis. The Src homology domain protein B (Shb) adaptor protein was recently implicated as a regulator of Th cell differentiation. Shb is an integral component of the T‐cell receptor (TCR) signalling complex and in the absence of <italic>Shb</italic> the TCR is less responsive to stimulation, resulting in the preferential development of Th2 responses under conditions of <italic>in vitro</italic> stimulation. In the present study, we extend those observations to an <italic>in vivo</italic> situation using a murine model of atopic dermatitis. <italic>Shb</italic> knockout mice develop more pronounced symptoms of atopic dermatitis with increased localized oedema, epidermal hyperplasia and IgE production. Dermal infiltration of mast cells, eosinophils, CD4⁺ Th cells and F4/80⁺ macrophages was also significantly increased in <italic>Shb</italic>‐deficient mice. This correlated with elevated transcription of the hallmark Th2 cytokines interleukin‐4 and interleukin‐5. The loss of <italic>Shb</italic> therefore alters TCR signalling ability, thereby favouring the development of Th2‐driven inflammation and exacerbating symptoms of allergy.</p> </abstract>