Polymorphisms of the Bcl-2 family member bfl-1 in children with atopic dermatitis.

T lymphocytes into theskin, and their longevity once there. These Tlymphocytes are key mediators of the chronicinflammatory response characteristic of thiscondition (1). Inhibition of apoptosis and thusprolonged survival of these immune effector cellsin the skin, but not blood, is important in thepathogenesis of AD (2). Topical corticosteroidand calcineurin inhibitors, effective in the treat-ment of AD have been shown to induce apop-tosis of cutaneous T lymphocytes (3).Lymphocyte apoptosis is regulated by intracel-lularproteins,whichincludemembersofthelargeBcl-2 family (4). Bfl-1 is a 175 amino acid Bcl-2member with anti-apoptotic activity (5, 6). It isunique in that rather than being constitutionallyexpressed, it is transcriptionally regulated bygrowth factors, such as granulocyte macrophage-colony stimulating factor (GM-CSF) and inflam-matory cytokines including tumour necrosisfactor (TNF)-a and interleukin (IL)-1b, all ofwhicharepresentinincreasedamountsintheskinof patients with AD (7–10). We have previouslyshown that polymorphisms in GM-CSF andtransforming growth factor (TGF-b) are associ-ated with a genetic predisposition to AD (11, 12).High levels of these factors in the skin mightinfluence Bfl-1 expression promoting survival ofactivated T lymphocytes and thus a chronicinflammatory response.The NC/Nga-inbred mouse strain is an animalmodel of human AD in that it spontaneouslydevelops dermatitis with many of the clinical,histological and immunological features of hu-man AD (13, 14). Experiments crossing NC/Ngamice and the MSM/MS strain that does notdevelop dermatitis have shown that the majorgenetic locus for the dermatitis phenotype mapsto a region of chromosome 9 (15). Althoughthe exact gene or genes responsible are still