The research laboratory of Baohua Zhou, PhD, studies the development and function of effector T helper (Th) cells and regulatory T (Treg) cells, and their impact on immune mediated inflammatory diseases.
Zhou was one of the leading researchers to discover the important role of the cytokine thymic stromal lymphopoietin (TSLP) in the pathogenesis of asthma. His lab also studies the imbalance of Th and Treg cells leading to chronic asthma and autoimmune diseases.
The role of skin-derived TSLP in promoting asthma development in infants with atopic dermatitisInfants with atopic dermatitis (AD) have an increased risk of developing asthma, but the underlying mechanisms of its development remain unclear. TSLP is mainly expressed by keratinocytes in the inflamed skin of patients with atopic dermatitis. In addition to promoting Th2/Th9 differentiation and memory generation, TSLP suppresses Treg differentiation even at low concentration. Thus one possible explanation for the increased asthma risk in infants with AD is that increased TSLP expression in these patients suppress allergen-specific Treg cells while promoting effector Th cell development in the airway mucosa—tipping the balance toward allergic responses that result in asthma. The Zhou Lab uses mouse models to test whether skin-derived TSLP breaks immune tolerance and induces allergic inflammation in the airway.
Alternative splicing and Treg functionA hallmark of higher eukaryotic gene expression is the pre-mRNA splicing during transcription. Alternative splicing of multi-exon genes not only regulates the stability, localization and translation of mature transcript by differential splicing the 5’ or 3’ UTRs, but also alters the protein structure, even the open reading frame of genes, and provides an important RNA-based layer of protein regulation and cellular function.
The Zhou Lab recently discovered that FOXP3, the master transcription factor for Treg development and function, interacts with splicing factors to regulate alternative splicing in Tregs. The research team is studying alternative splicing of human FOXP3 and mouse FOXP3 genes to investigate how the alternative splicing of human FOXP3 contributes to pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE), Type 1 diabetes and chronic asthma.
TSLP in Th2 Immunity and Allergic Airway Inflammation
Overall goal: Using mouse models to define the roles of TSLP in Th2 sensitization and inflammation.
Du, J., Wang, Q., Ziegler, S.F., and Zhou, B. (2018) FOXP3 interacts with hnRNP F to modulate pre-mRNA alternative splicing. J. Biol. Chem. 293:10235-10244.
Zeng, W.P., McFarland, M.M., Zhou, B., Holtfreter, S., Flesher, S., Cheung, A., and Mallick, A. (2017) Staphylococcal enterotoxin A-activated regulatory T cells promote allergen-specific TH2 response to intratracheal allergen inoculation. J Allergy Clin Immunol. 139:508-518.
Wang, Q., Du, J., Zhu, J. , Yang, X. and Zhou, B. (2015) Thymic stromal lymphopoietin signaling in CD4+ T cells is required for TH2 memory. J. Allergy Clin. Immunol. 135: 781-791.
Sehra, S., Yao, W., Nguyen, E.T., Glosson-Byers, N.L., Akhtar, N., Zhou, B., and Kaplan, M.H. (2015). Th9 cells are required for tissue mast cell accumulation during allergic inflammation. J Allergy Clin Immunol. 136:433-440.
Yao, W., Zhang, Y., Jabeen, R., Nguyen, E.T., Wilkes, D.S., Tepper, R.S., Kaplan, M.H. and Zhou, B. (2013) IL-9 is Required for TSLP-mediated Allergic Airway Inflammation. Immunity. 38:360-372.
