Absence of the adaptor protein Shb potentiates the TH2 response in a mouse model of atopic dermatitis
2014 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 143, no 1, 33-41 p.Article in journal (Refereed) Published
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 Shb the TCR is less responsive to stimulation, resulting in the preferential development of Th2 responses under conditions of in vitro stimulation. In the present study, we extend those observations to an in vivo situation using a murine model of atopic dermatitis. Shb 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 Shb-deficient mice. This correlated with elevated transcription of the hallmark Th2 cytokines interleukin-4 and interleukin-5. The loss of Shb therefore alters TCR signalling ability, thereby favouring the development of Th2-driven inflammation and exacerbating symptoms of allergy.
Place, publisher, year, edition, pages
2014. Vol. 143, no 1, 33-41 p.
atopic dermatitis, Th2 responses, T cell receptor signaling
Cell and Molecular Biology
Research subject Medical Cell Biology
IdentifiersURN: urn:nbn:se:uu:diva-209338DOI: 10.1111/imm.12286ISI: 000340385000004OAI: oai:DiVA.org:uu-209338DiVA: diva2:656793