Nicholas W. Lukacs, Ph.D.
Professor of Pathology
Assistant Dean for Research Faculty
http://www.pathology.med.umich.edu/index.php?t=page&id=456

nlukacs@umich.edu

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.

Representative Publications

Lukacs, N.W. Role of chemokines in the pathogenesis of asthma. Nature Reviews Immunology 1:108-116, 2001.

N.W. Lukacs, D. M. Prosser, S. A. Lira, and D. N. Cook. Requirement for the chemokine receptor CCR6 in allergic pulmonary inflammation. J. Exp. Med. 20;194(4):551-6, 2001 .

Sandra H.P. Oliveira, D.D. Taub, J. Nagel, R. Smith, and N.W. Lukacs. Stem cell factor (SCF) induces eosinophil activation and degranulation: mediator and gene array analysis. Blood 100(13):4291-7, 2002 .

Lukacs, N.W., A.L. Miller, and C.M. Hogaboam. Chemokine receptors in Asthma: Searching for the correct immune targets. J. Immunol. 171(1):11-15, 2003.

Alison E. John, Craig J. Gerard, Allison L. Miller, Aaron A. Berlin, Matthew A. Schaller, Allison A. Humbles, and Nicholas W. Lukacs. Respiratory syncytial virus induced exaggeration of allergic airway disease is dependent upon CCR1-associated immune responses. Eur. J. Immunol. 35(1):108-16, 2004.

Brian D. Rudd, Ezra Burstein, Colin Duckett, Xiaoxia Li, and Nicholas W. Lukacs. Differential role of TLR3 in RSV induced chemokine expression. J. Virology 79(6):3350-7, 2005 .

Steven K. Lundy, Sergio A. Lira, Donald N. Cook, Aaron A. Berlin, and Nicholas W. Lukacs. Attenuation of allergen-induced responses in CCR6-/- mice is dependent upon altered pulmonary T lymphocyte activation. J. Immunol. 174(4):2054-60, 2005.

Matthew A. Schaller, Steven K. Lundy, Gary B. Huffnagle 1 , and Nicholas W. Lukacs. Tc2: CD8 + T cell contributions to type 2 mediated eosinophil response and airway hyperreactivity. Eur. J. Immunol. 35(7):2061-70, 2005 .

Jetse J. Smit, Brian D Rudd, and Nicholas W. Lukacs. Plasmacytoid Dendritic cells modulate the pulmonary immune response and clearance of respiratory syncytial virus. J. Exp. Med. 2006. 2 03:1153-9.

Rudd, BD, MA Schaller, JJ Smit, SL Kunkel, R. Neupane, L. Kelley, AA Berlin, and NW Lukacs. MyD88-Mediated Instructive Signals in Dendritic Cells Regulate Pulmonary Immune Responses during Respiratory Virus Infection. J Immunol. 2007, 178(9):5820-7.

Matthew A. Schaller, Rupak Neupane, Brian D. Rudd, Steven L. Kunkel, Lara E. Kallal, Pamela Lincoln, John B. Lowe, Yunfang Man, and Nicholas W. Lukacs.  Notch Ligand Delta-like 4 regulates diseases pathogenesis during respiratory viral infections by modulating Th2 cytokines.  J. Exp. Med. 204(12):2925-34, 2007.

Smit, JJ, Lindell, DM, Boon, L, Kool, M, Lambrecht, BN, and Lukacs, NW.  The balance between plasmacytoid DC versus conventional DC determines pulmonary immunity to virus infections.  PLoS One, 2008. 3:e1720.

Mukherjee, S., Schaller, MA, Neupane, R, Kunkel, SL, and Lukacs, NW. Regulation of T cell activation by Notch ligand, DLL4, promotes IL-17 production and Rorc activation. 2009. J. Immunol. 182:7381-88.

Vladislav Dolgachev, Bryan C. Petersen, Alison L. Budelsky, Aaron A. Berlin, and Nicholas W. Lukacs. Pulmonary IL-17E (IL-25) production and IL-17RB+ myeloid cell-derived TH2 cytokine production are dependent upon SCF-induced responses during chronic allergic pulmonary disease. 2009 J. Immunol. 183:5705-15.

Kallal LE, Schaller MA, Lindell DM, Lira SA, Lukacs NW.  CCL20/CCR6 blockade enhances immunity to respiratory syncytial virus by impairing recruitment of dendritic cells. Eur. J. Immunol. 183(10):6698-707. 2010.

Nicholas W. Lukacs, Joost J. Smit, Sumanta Mukherjee, Susan B. Morris, Gabriel Nunez, and Dennis M. Lindell. Respiratory Virus-induced TLR7 activation controls IL-17-associated increased mucus via IL-23 regulation.  J. Immunol. 2010.

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. 

Bryan C. Petersen, Alison L. Budelsky, Alan P. Baptist, Matthew A. Schaller, and Nicholas W. Lukacs. 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