PGE₂ Regulation of B Lymphocytes and T Helper 1 and T Helper 2 Cells: Induction of Inflammatory versus Allergic Responses

Abstract

Immunoglobulin E (IgE) and T-helper type 2 (Th2) cytokines mediate many traits of allergic disease. Therefore, understanding regulation of these responses is critical for comprehending disease pathogenesis and for developing effective therapies. Numerous mechanisms regulate IgE and Th2 cytokine production, however, an emerging concept is that E-series prostaglandins (PGEs), shift the immune response towards allergy by promoting production of IgE and a Th2 profile of cytokines (1). PGEs are lipid molecules which regulate diverse processes throughout the body. Low levels of PGEs are constantly produced in most tissues by “constitutive” cyclooxygenases (COX-1), (2). In response to hormonal or inflammatory stimuli, PGEs are also synthesized by “inducible” cyclooxygenases (COX-2), (2). Of particular importance, PGEs are a major product of professional antigen presenting cells such as, macrophages, follicular dendritic cells and Langerhans cells (1, 2). PGEs are also produced by other APCs such as, fibroblasts and endothelial cells in response to inflammatory stimuli (2). PGEs promote IgE and Th2 responses at multiple levels. Firstly, PGEs induce development of Th2 cells via modulating cytokine production by antigen presenting cells. Secondly, PGEs inhibit Th1 and promote Th2 profiles of cytokine production from mature differentiated T cells. Finally, PGEs directly target B lymphocytes and enhance cytokine-directed recombination of the Ig heavy chain loci.