Lukacs Laboratory

Home Lab Members Dendritic Cell Biology Early Life RSV Infection Epigenetics Mast Cell Biology & SCF Microbiome Contact Information

Additional Information

Molecular & Cellular Pathology Immunology Graduate Program PIBS Lukacs Lab Publications

University of Michigan

University of Michigan NIH
  1. Home

Welcome

Over the past several years, our laboratory research has been focused on the immunologic mechanisms involved in the development of asthma and respiratory virus infections.  The basic research in the lab has identified numerous targets that are being pursued for alleviating chronic pulmonary disease and at the same time we continue to gain a better understanding of how pulmonary immune responses develop. We have established animal models of pulmonary disease that allow us to ask basic mechanistic questions as well as perform pre-clinical assessments of pharmacologic targets. Our model of allergic airway disease that recapitulates several clinical features of allergic asthma is induced using a cockroach skin test antigen that elicits a strong Th2 skewed response with characteristic eosinophil accumulation and mucus overproduction, as depicted below. The areas investigated using this airway model include mast cell biology, eosinophilic inflammation, dendritic cell biology, and T lymphocyte activation and differentiation. The proper development of the immune system in infants is central to establishing a balanced response that reacts appropriately to infectious stimuli but does not develop pathogenic responses.  One of the first signs of an inappropriate and potentially pathogenic immune response in children is manifested by Respiratory Syncytial Virus (RSV) infection, which is the most prominent cause of childhood hospitalization. We have demonstrated that early-life RSV (EL-RSV) infection of the lungs modifies the development of systemic immune responses in neonates that can lead to exacerbated asthmatic responses later in life.

In addition, the EL-RSV infection leads to long-term changes in the microbiome that accompany the altered immune responses. These findings reflect clinical data from infants and indicate that both lung and gut microbiomes are altered in infants with severe RSV infections. However, whether and how the microbiome alters the host immune and physiologic response locally in the lungs and/or systemically is unknown and is being actively addressed. We have also established that the early events induced by RSV infection modify the progression of allergic responses later in life through the long-term alteration of immune cell phenotypes by epigenetic mechanisms and accompanying lung structure/function alterations. The investigation of the mechanisms that govern these responses will establish new paradigms and will fill in a significant gap in our understanding of the developing neonatal immune system and pulmonary disease.  Our previous studies have helped to link persistent innate immune cells, DCs and ILC2, to the development of a pro-asthmatic, Th2 lung environment later in life.  Our published data establish that RSV responses and changed microbiome are associated with altered systemic metabolite profiles and together alter lung function long term. Our data further demonstrates probiotic supplementation with Lactobacillus johnsonii can attenuate the altered long-term lung function changes. Altogether, our studies attempt to highlight how early life environmental factors can shape ongoing and chronic disease by systemic immune modulatory events.