Nicholas W. Lukacs,
Godfrey Dorr Stobbe Professor of Research
Professor of Pathology
Assistant Dean for Research Faculty
Over the past several years our laboratory research has focused on the interrelationship of cytokines, chemokines, and leukocyte activation during asthmatic-type airway and Th1/Th2 type immune responses. The development of a clinically relevant mouse cockroach allergen-induced airway model that demonstrates a number of in vivo correlates to human asthma has been successfully utilized to further elucidate novel mechanisms of pulmonary inflammation. The areas that have been successfully investigated using the allergic airway models include mast cell biology, eosinophilic inflammation, and T lymphocyte activation. In addition, we also examine the role of pulmonary viral infections (Respiratory Syncytial Virus; RSV) on exacerbation and increased development of allergic asthmatic responses. Using these models, we have specifically identified particular leukocyte populations that have an effect during different stages of asthmatic-like responses within the lung. Our most recent research has centered upon the role of important innate immune molecules that direct the direction of the immune response using defined mechanisms of activation. In particular, the toll-like receptor (TLR) system and a novel Notch ligand mediated activation of T lymphocytes has led to a number of important mechanistic studies.
Mukherjee, S., DM Lindell, AA Berlin, SB Morris, TP Shanley, MB Hershenson, and NW Lukacs. IL-17-induced pulmonary pathogenesis during respiratory viral infection and exacerbation of allergic disease. Amer. J. Pathol. 2011. 179(1):248-58.
Morris, S., MS Swanson, A Lieberman, M. Reed, Z. Yue, DM Lindell, and NW Lukacs. Autophagy-mediated DC activation is essential for innate cytokine production and APC function with Respiratory Syncytial Virus responses. J. Immunol. 187(8):3953-61 2011.
Petersen BC, Budelsky AL, Baptist AP, Schaller MA, Lukacs NW. IL-25 induces type 2 cytokine production in a novel, steroid resistant IL-17RB+ myeloid population that exacerbates asthmatic pathology. Nature Medicine. 2012 Apr 29. 18(5):751-8
Demoor T, Petersen BC, Morris S, Mukherjee S, Ptaschinski C, De Almeida Nagata DE, Kawai T, Ito T, Akira S, Kunkel SL, Schaller MA, Lukacs NW. IPS-1 signaling has a nonredundant role in mediating antiviral responses and the clearance of respiratory syncytial virus. J. Immunol. 2012, 189:5942-53.
Reed M, Morris SH, Jang S, Mukherjee S, Yue Z, and Lukacs NW. Autophagy-inducing protein Beclin-1 dendritic cells regulate CD4 T cell responses and disease severity during Respiratory Syncytial Virus Infection. 2013. J. Immunol. 191:2526-37.
Fujimura KE, Demoor T, Rauch M, Faruqi AA, Jang S, C Johnson C, Boushey HA, Zoratti E, Ownby D, Lukacs NW*, Lynch SV: House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection. Proceedings of the National Academy of Sciences of the United States of America: 111(2):805-10. 2014. (*co-corresponding author)
de Almeida Nagata DE, Demoor T, Ptaschinski C, Ting HA, Jang S, Reed M, Mukherjee S, Lukacs NW: IL-27R-Mediated Regulation of IL-17 Controls the Development of Respiratory Syncytial Virus Associated Pathogenesis. The American journal of pathology: 184(6):1807-18. 2014.