|
SELECTED ARTICLES FROM THE RECENT LITERATURE 2008
8/15/2008
TH2 adjuvants
Summary
The purpose of this study was to investigate pathways by which aeroallergen (house dust mite) and the TH2 adjuvant, cholera toxin, promote a shift to TH2 and TH17 mediated immune responses. The investigators demonstrated that house dust mite and cholera toxin induce cell surface expression of c-Kit and its ligand, stem cell factor, on dendritic cells. The upregulation of c-Kit and stem cell factor caused downstream signaling that promoted IL-6 production in a mouse model. IL-6 production in turn upregulated TH2 and TH17 responses.
When c-Kit mutant mice were employed or neutralization of IL-6 was accomplished, there was blunting of the TH2 and TH17 upregulation. In addition, lower amounts of IL-6 were produced if dendritic cells lacking functional c-Kit or unable to express membrane receptor stem cell factor were utilized.
The TH1 adjuvant, CpG oligodeoxynucleotide, failed to enhance c-Kit expression in this model. In addition, dendritic cells from mice expressing an inactive form of the p110 subunit of phosphatidylinositol-3 kinase produced lower amounts of IL6 upon stimulation by cholera toxin.
The authors interpreted these data as highlighting the importance of the IL-6 signaling pathway in regulating T-cell responses. The article also noted the role of phosphatidylinositol-3 kinase in this regard as well.
Editor's Comments
In a recent issue of The Journal of Allergy and Clinical Immunology (121[6], June 2008), Berin and Shreffler discussed the role of TH2 adjuvants in promoting TH2 and TH17 inflammatory immune responses. This article mentioned notch signaling, the phosphatidylinositol pathway, and cholera toxin. These substances enhance the potential for IgE-mediated inflammation. This mouse model confirms the importance of these "adjuvants" in IgE-mediated inflammation.
Reference
Krishnamoorthy N, et al. Activation of c-Kit in dendritic cells regulates T helper cell differentiation and allergic asthma. Nature Medicine 2008; 14:565-573.
|