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allergic airways disease • type 2 inflammation • group 2 innate lymphoid cells • cell penetrating peptides • animal models
We use murine models of allergic airways disease to better understand how innate and adaptive immunity coordinate to promote type 2 inflammation in the lung. We are currently examining how innate cells in the lung, activated by IL-33 in adult mice, or respiratory syncytial virus (RSV) in young mice, promote type 2 inflammation and Th2 adaptive immunity. One focus of our work is to better understand how STAT6 activation in eosinophils promotes their activity. As part of our program to understand the link between innate and Th2 adaptive immunity in the lung, we are characterizing activity of an immunomodulatory peptide we developed (STAT6-IP). We have also developed murine models of atopic dermatitis to extend these studies. Finally, we are characterizing how sex and sex hormones influence each of these outcomes.
Srinivasa, B.T., K.H. Restori, J. Shan, L. Cyr, L. Xing, S. Lee, B.J. Ward, and E.D. Fixman. (2017) STAT6 inhibitory peptide given during RSV infection of neonatal mice reduces exacerbated airway responses upon adult re-infection. J Leuk Biol 101:519-529.
Restori, K.H., B.T. Srinivasa, B.J. Ward, E.D. Fixman. (2018) Neonatal immunity, respiratory virus infections, and the development of asthma. Front Immunol 9:1249.
Guak, H., S. Al Habyan, E.H. Ma, H. Aldossary, M. Al-Masri, S.Y. Won, T. Ying, E.D. Fixman, R.G. Jones, L.M. McCaffrey, and C.M. Krawczyk. (2018) Glycolytic metabolism is essential for CCR7 oligomerization and dendritic cell migration. Nat Commun 9:2463.
Lee, S., J. Shan, H. Aldossary, V. Gaudreault, M. Bazett, E.D. Fixman. (2019) STAT6 inhibitory peptide reduces dendritic cell migration to the lymph nodes to control Th2 adaptive immunity in the mouse lung. Eur J Immunol. 49:157-169.
Zhao H, V Moarbes, V Gaudreault, J Shan, H Aldossary, ED Fixman (2019) Sex differences in IL-33-induced STAT6-dependent type 2 airway inflammation. Front Immunol 10:859.