Airway epithelium in innate and adaptive immune responses
The research focus of the Poynter lab is to investigate the role of the airway epithelium in the initiation and modulation of innate and adaptive immune responses. In particular, we focus on the genesis of allergic asthma, attempting to determine how environmental components can cause the development of an allergic response against an otherwise innocuous inhaled antigen. The model environmental compound we study, nitrogen dioxide (NO2), is an oxidant gas that can be generated endogenously or as a product of combustion processes. Furthermore, epidemiologic evidence indicates that individuals exposed to elevated levels of NO2 have an increased liklihood of developing asthma as well as having more severe disease. The understanding gained into the initiation of allergy is also used in the lab to develop and test novel therapeutic approaches in preclinical models.
The Poynter laboratory is interested in the myriad of ways in which pulmonary innate and adaptive immune responses are initiated and modulated in response to environmental gasses, components of infectious organisms, and allergens.
The airway epithelium constitutes a first line of defense against inhaled materials. As such, the epithelium must be responsive to these materials and activate signal transduction cascades that induce expression of genes modulating local defenses, the recruitment and activation of innate immune inflammatory cells, including dendritic cells, as well as cells of the adaptive immune system, especially CD4+ T lymphocytes. Thereby, products of activated airway epithelial cells may modulate the initiation and polarization of T cell-dependent immune responses that serve to protect the host from infection or cause pathology in pulmonary disease..
Through an understanding of the pathology of disease using mouse models, in vitro systems, and human tissues we hope to apply our research findings to prevention and treatment of the allergic airway disease, asthma, as well as to the development of adjuvants for mucosal and systemic vaccination via inhalation.
Ongoing projects in the Poynter lab focus on the role of the airway epithelium in initiation and modulation of innate and adaptive immune responses
Central role for airway epithelial NF-kappaB activation in NO2-induced allergic sensitization
Ather, J.L., Alcorn, J.F., Brown, A.L., Guala, A.S., Suratt, B.T., Janssen-Heininger, Y.M.W., and M.E. Poynter. Distinct functions of airway epithelial NF-B activity regulate nitrogen dioxide-induced acute lung injury. American Journal of Respiratory Cell and Molecular Biology, 2009 Oct;43(4):443-51, PMC2951874.
Paveglio, S.A., Allard, J., Mayette, J., Whittaker, L.A., Juncadella, I., Anguita, J., and M.E. Poynter. The tick salivary protein, Salp15, inhibits the development of experimental asthma. Journal of Immunology, 178(11): 7064-7071 (2007).
Bevelander, M., Mayette, J., Whittaker, L.A., Robbins, J., Hemenway, D., and M.E. Poynter. Nitrogen dioxide promotes allergic sensitization to inhaled antigen. Journal of Immunology, 179(6): 3680-3688 (2007).
Paveglio, S.A., Allard, J., Foster, S.R., Ather, J., Bevelander, M., Mayette, J., Whittaker, L.A., McCarthy, S.M., van der Vliet, A., Suratt, B.T., Boyson, J.E., and M.E. Poynter. Airway epithelial indoleamine 2,3-dioxygenase inhibits CD4+ T cells during Aspergillus fumigatus antigen exposure. American Journal of Respiratory Cell and Molecular Biology, 2011 Jan;44(1):11-23, PMC3028254.
Hodgkins, S.R., Ather, J.A., Paveglio, S.A., Allard, J.L., Whittaker LeClair, L.A., Suratt, B.T., Boyson, J.E., and M.E. Poynter. NO2 inhalation induces maturation of pulmonary CD11c+ cells that promote antigen-specific CD4+ T cell polarization in the lung. Respiratory Research, 2010, 11:102, PMC2918560.
Poynter, M.E., Cloots, R., van Woerkom, T., Butnor, K.J., Vacek, P., Taatjes, D.J., Irvin, C.G., and Y.M.W. Janssen-Heininger. NF-kappaB Activation in Airways Modulates Allergic Inflammation but not Hyperresponsiveness. Journal of Immunology, 173: 7003-7009 (2004)
Allard, J.B., Poynter, M.E., Marr, K.A., Cohn, L., Rincon, M., L.A. Whittaker. Aspergillus fumigatus generates an enhanced Th2-biased immune response in mice with defective cystic fibrosis transmembrane conductance regulator. Journal of Immunology 2006 Oct 15; 177(8):
* indicates equal contribution
Ather JL, Martin RA, Ckless K, Poynter ME (2014) Inflammasome Activity in Non-Microbial Lung Inflammation. J Environ Immunol Toxicol 1(3): 108-117.
Randall MJ, Kostin SF, Burgess EJ, Hoyt LR, Ather JL, Lundblad LK, Poynter ME (2014) Anti-inflammatory effects of levalbuterol-induced 11β-hydroxysteroid dehydrogenase type 1 activity in airway epithelial cells. Front Endocrinol (Lausanne) 5: 236.
Ather JL, Foley KL, Suratt BT, Boyson JE, Poynter ME (2015) Airway epithelial NF-κB activation promotes the ability to overcome inhalational antigen tolerance. Clin Exp Allergy in press.
Pothen JJ, Poynter ME, Bates JH (2015) A computational model of unresolved allergic inflammation in chronic asthma. Am J Physiol Lung Cell Mol Physiol 308(4): L384-90.
Nolin JD, Tully JE, Hoffman SM, Guala AS, van der Velden JL, Poynter ME, van der Vliet A, Anathy V, Janssen-Heininger YM (2014) The glutaredoxin/S-glutathionylation axis regulates interleukin-17A-induced proinflammatory responses in lung epithelial cells in association with S-glutathionylation of nuclear factor κB family proteins. Free Radic Biol Med 73: 143-53.
Martin RA, Hodgkins SR, Dixon AE, Poynter ME (2014) Aligning mouse models of asthma to human endotypes of disease. Respirology 19(6): 823-33.
Hoffman SM, Tully JE, Nolin JD, Lahue KG, Goldman DH, Daphtary N, Aliyeva M, Irvin CG, Dixon AE, Poynter ME, Anathy V (2013) Endoplasmic reticulum stress mediates house dust mite-induced airway epithelial apoptosis and fibrosis. Respir Res 14: 141.
Invited lecturer, IDeA Centers of Biomedical Research Excellence (CoBRE) Program, Annual Principal Investigators Meeting Invited lecturer, “Mentoring: From the Mentee’s Perspective”, IDeA Centers of Biomedical Research Excellence (CoBRE) Program, 2004 Annual Principal Investigators Meeting, National Institutes of Health, Bethesda, MD, November 8-9, 2004. (November 8-9, 2004)
American Thoracic Society Young Investigator Delegate to the 46th Annual Meeting of the Japanese Respiratory Society, Tokyo, JAPAN American Thoracic Society Young Investigator Delegate to the 46th Annual Meeting of the Japanese Respiratory Society, Invited lecturer, “Nitrogen Dioxide (NO2)-Induced Allergic Sensitization to Inhaled Antigens Requires Toll-Like Receptor (TLR)2”, Tokyo, JAPAN, June 2006. (June, 2006)
Department of Medicine
Office: E410A Given
Lab: E405 Given
Ed Burgess, CMB Student
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- 4/14/2015 11:30 AM – 12:30 PM
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