Allergic dysregulation and hyperimmunoglobulinemia e in Foxp3 mutant mice

Citations of this article
Mendeley users who have this article in their library.


Background: Regulatory T cells have been proposed to play an important role in regulating allergic inflammation. The transcription factor Foxp3 is a master switch gene that controls the development and function of natural and adaptive CD4+CD25+ regulatory T (TR) cells. In human subjects loss-of-function Foxp3 mutations trigger lymphoproliferation, autoimmunity, and intense allergic inflammation in a disease termed immune dysregulation polyendocrinopathy enteropathy-X-linked syndrome. Objective: We sought to examine the evolution and attributes of allergic inflammation in mice with a targeted loss-of-function mutation in the murine Foxp3 gene that recapitulates a known disease-causing human Foxp3 mutation. Methods: Foxp3 mutant mice were generated by means of knock-in mutagenesis and were analyzed for histologic, immunologic, and hematologic abnormalities. The role of signal transducer and activator of transcription 6 (Stat6) in disease pathogenesis was analyzed by using Stat6 and Foxp3 double-mutant mice. Results: Foxp3 mutant mice developed an intense multiorgan inflammatory response associated with allergic airway inflammation, a striking hyperimmunoglobulinemia E, eosinophilia, and dysregulated TH1 and TH2 cytokine production in the absence of overt TH2 skewing. Concurrent Stat6 deficiency reversed the hyperimmunoglobulinemia E and eosinophilia and delayed mortality, which is consistent with a pathogenic role for allergic inflammation in Foxp3 deficiency. Conclusion: Allergic dysregulation is a common and fundamental consequence of loss of CD4+CD25+ TR cells caused by Foxp3 deficiency in different species. Abnormalities affecting TR cells might contribute to a variety of allergic diseases. © 2005 American Academy of Allergy, Asthma and Immunology.




Lin, W., Truong, N., Grossman, W. J., Haribhai, D., Williams, C. B., Wang, J., … Chatila, T. A. (2005). Allergic dysregulation and hyperimmunoglobulinemia e in Foxp3 mutant mice. Journal of Allergy and Clinical Immunology, 116(5), 1106–1115.

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free