Lee J. Quinton, Ph.D.
Associate Professor of Medicine and Pathology
- The acute phase response
- Cytokine regulation
- Acute lung injury
Lung infections account for a tremendous burden of disease, representing the most frequent cause of infection-related deaths and a common cause of acute lung injury. The innate immune response is critical for the prevention of lower respiratory tract infections. Yet, this response must be tightly regulated, such that adequate host defenses do not result in inflammatory lung injury.
Our long-term goal is to elucidate intra- and extra-pulmonary signaling events required for an immune response that is both effective and balanced. The local response to lung infections includes neutrophil recruitment, expression of soluble mediators such as cytokines, and the extravasation of plasma constituents from the vascular space into the alveolar space. The result is an inflammatory milieu and cellular composition that promotes local immune responsiveness. This physiologic transition within the lung, however, occurs in tandem with a systemic acute phase response (APR), typified by altered circulating levels of acute phase proteins (APPs). While the APR has long been recognized as a useful biomarker of disease progression during pneumonia, the collective impact of APPs on inflammation and host defense are unknown. We have previously shown that the cytokines TNF-alpha, IL-1, and IL-6, which are critical for maximal host defense during pneumonia, are also essential for the activation of downstream transcription factors and the expression of APPs in the liver. Therefore, the hepatic APR may be a systemic conduit through which select cytokines promote the immune response to lung infection. Understanding how APPs and other extra-pulmonary factors integrate with local responses in the lung to promote immunity and tissue protection during pneumonia will help to identify novel prognostic indicators and therapeutics for this important disease.
In addition to the acute phase response, our laboratory is also interested in local factors controlling innate immunity and inflammation within the airspaces of infected lungs. We have previously shown that signaling downstream of the transcription factor STAT3 is essential for tissue protection during pneumonia. We are now particularly interested in the degree to which leukemia inhibitory factor (LIF), a STAT3-signaling cytokine, is responsible for calibrating acute pulmonary inflammation during pneumonia.
- Hilliard, K.L., Allen, E., Traber, K.E., Kim, Y., Jones, M.R., Mizgerd, J.P., and Quinton, L.J. (corresponding author). (2015) Activation of hepatic STAT3 maintains pulmonary defense during endotoxemia. Infection and Immunity 83(10): 4015-27
- Traber, K.E., Allen, B.A., Hilliard, K.L., Yamamoto, K., Jones, M.R., Mizgerd, J.P., and Quinton, L.J. (corresponding author). (2015) Oncostatin M is required for maximal CXCL5 expression and neutrophil recruitment during pneumonia. American Journal of Respiratory Cell and Molecular Biology 55(4): 479-88
- Hilliard, K.L., Allen, E., Traber, K.E., Yamamoto, K., Stauffer, N.M., Wasserman, G.A., Jones, M.R., Mizgerd, J.P., and Quinton, L.J. (corresponding author). (2015) The lung-liver axis facilitates pulmonary innate immunity and hepatoprotection during pneumonia. American Journal of Respiratory Cell and Molecular Biology 53(3): 378-90
- Quinton LJ and Mizgerd JP (2014) Dynamics of lung defense in pneumonia: resistance, resilience, and remodeling. Annual Reviews in Physiology 77: 407-30
- Ahyi AN, Quinton LJ, Jones MR, Ferrari JD, Pepper-Cunningham ZA, Mella JR, Remick DG, and Mizgerd JP (2013) Roles of STAT3 in protein secretion pathway during the acute phase response. Infection and Immunity 81(5): 1644-53
- Quinton LJ (corresponding author), Mizgerd JP, Hilliard KL, Jones MR, Kwon CY, and Allen E (2012) Leukemia inhibitory factor signaling is required for lung protection during pneumonia. Journal of Immunology 188 (12): 6300-8
- Quinton LJ (co-corresponding author), Blahna MT, Jones MR, Allen E, Hilliard KL, Ferrari JD, Zhang X, Sabharwal V, Algul H, Akira S, Schmid RM, Pelton SI, Spira A, and Mizgerd JP (2012) Combined hepatocyte-specific targeting of NF-κB RelA and STAT3 abrogates the acute phase response in mice. Journal of Clinical Investigation 122 (5): 1758-63
- Quinton, L.J., Jones, M.R., Robson, B.E., and Mizgerd, J.P. (2009) Mechanisms of the hepatic acute phase response during bacterial pneumonia. Infection and Immunity 77: 2417-26
- Quinton, L.J., Jones, M.R., Robson, B.E., Simms, B.T., Whitsett, J.A., and Mizgerd, J.P. (2008) Alveolar epithelial STAT3, IL-6 family cytokines, and host defense during Escherichia coli pneumonia. American Journal of Respiratory Cell and Molecular Biology. 38 (6): 699-706
- Quinton, L.J., Jones, M.R., Simms, B.T., Kogan, M.S., Robson, B.E., Wilson, C.B., Skerrett, S.J., and Mizgerd, J.P. (2006) Functions and regulation of NF-kB RelA during pneumococcal pneumonia. Journal of Immunology. 178: 1896-1903
- Mechanisms of the hepatic acute phase response during bacterial pneumonia
- Alveolar epithelial STAT3, IL-6 family cytokines, and host defense during Escherichia coli pneumonia
- Functions and regulation of NF-kB RelA during pneumococcal pneumonia