Triggering through CD40 promotes interleukin‐4‐induced CD23 production and enhanced soluble CD23 release in atopic disease

Abstract

The pathogenesis of atopic disease is closely linked to the overproduction of IgE. CD23 and CD40 are two cellular receptors involved in the regulation of IgE production and both receptors are elevated in atopic disease. We have examined the role of CD40 in the regulation of CD23 and soluble CD23 production in healthy and atopic donors. Triggering of the B cell CD40 receptor directly enhances interleukin (IL)-4-mediated up-regulation of CD23 at both the protein and the mRNA level. When atopic donors were studied, the synergistic effect of CD40 triggering on the IL-4-induced up-regulation of CD23 and soluble CD23 (sCD23) was enhanced and there was a relative skewing toward production of sCD23. These studies implicate the CD40 receptor in the hyperproduction of CD23 and sCD23 in atopic disease and suggest that abnormalities may exist in the cellular pathways leading to sCD23 production.

Allergen‐mediated modulation of CD23 expression is interferon‐γ and interleukin‐10 dependent in allergic and non‐allergic individuals

“…By contrast, increased CD23 expression by B cells was observed after direct ex vivo analysis in patients suffering from atopic dermatitis [31]. Paterson et al [32] also did not find differences of surface expression and sCD23 release after 2 days of unstimulated culture, although they describe a larger increase in allergics than in non‐sensitized individuals after stimulation with IL‐4 and IL‐4/CD40. Controversial data have been published by Corominas et al [33] with no differences in CD23 or sCD23, but differing results in an earlier publication [34].…”

Differential B‐lymphocyte regulation by CD40 and its viral mimic, latent membrane protein 1

“…Soon after the discovery of CD40, it was implicated as playing an important causal role in collagen‐induced arthritis (CIA), a mouse model of human rheumatoid arthritis (RA) (219), and was soon implicated in mouse models of systemic lupus erythematosus (SLE) (220–222) and multiple sclerosis models (223, 224) as well. CD40 involvement was subsequently implicated in allergic diseases, autoimmune diabetes, and Graves’ disease, an autoimmune thyroiditis (225–227). CD40 has also been demonstrated to play roles in psoriasis and inflammatory bowel diseases (reviewed in 218).…”

Stress molecules in sepsis and systemic inflammatory response syndrome

“…More recently, IL‐1 receptor antagonist (IL‐1Ra), LPS binding protein (LBP), and soluble CD14 were identified as acute‐phase proteins. However, IL‐6 may induce myocardial depression during septic shock, as shown during meningococcemia [14].…”