My research includes intestinal host defense: immune tolerance and immune protection in inflammatory bowel disease, HIV or SARS-CoV-2 infection, and opioid use disorder.
Research Information
Research Projects
Intestinal Host Defense: Toggling between immune tolerance and immune protection
The intestinal mucosa is the largest lymphoid organ, as assessed by the quantity of antibody produced, the number of resident leukocytes, and its surface area exposure to the environment (greater than that of a tennis court). Confounding the situation, the wall of the gut is continuously bathed by bacteria, parasites, fungi, amoebae, viruses, mitogens, toxins, and immunogenic food proteins. Therefore, a complex multi-tiered host defense system has evolved in the gut that can be divided into four interactive functions:
- Barrier exclusion by an actively regenerating epithelial cell monolayer.
- Innate inflammatory responses mediated by local synthesis of pro- and anti-inflammatory cytokines and antimicrobial peptides.
- Acquired immune responses regulated by T lymphocytes.
- Host-microbiome colonization and differentiation.
Our laboratory focuses on the mechanisms that regulate these systems:
- Effects on intestinal permeability associated with HIV infection or inflammatory bowel disease (IBD), due to changes in the the structure, composition, and function of the tight junctional complex that regulates paracellular epithelial continuity.
- In murine models of acute and chronic intestinal inflammation, we investigate the temporal expression and regulation of pro-inflammatory and anti-inflammatory cytokines in response to gut injury induced by ischemia associated with illicit drug abuse (opioids, methamphetamine, cocaine), and in a transgenic mouse that models human inflammatory bowel disease.
- Dysbiosis in the HIV+, drug abuse, or IBD gut, and its consequent effect on host mucosal immune protection.
- Using transgenic murine models, we explore the mechanisms by which co-stimulatory and accessory molecules direct the development of immune tolerance as T cells migrate from the Peyer's patch to the gut wall.
- We characterize the biochemical, spatial, temporal, and structural organization of the signal transduction pathway initiating with the anti-specific T cell receptor, and differentially regulated in naïve, helper, effector, and mucosal T cells.
- We research the regulation of integrin affinity/avidity, expression, and activation in both naïve and memory T cells by the interstitial extracellular matrix, and how matrix-induced T cell polarization modulates the partitioning of the TCR/CD3 signaling complex in the plasma membrane.
Publications
Chung C.Y., Alden S.L., Fu P., Funderburg N.T., Levine A.D. "." PLoS Pathog (2014) 10:e1004198; doi: 10.1371/journal.ppat.1004198. PMCID: PMC4072797.
Gill, T., Levine, A.D. "." J. Biol Chem (2013) 288, 26246-26255; doi: 10.1074/jbc.M113.476895. Published online July 23, 2013. PMCID: PMC3764828
Meisch, J.P., Vogel, R.M., Schlatzer, D.M., Li, X., Chance, M.R., Levine, A.D. "." J Leukoc Biol (2013) 94, 459-471; doi:10.1189/jlb.0612300. Published online June 26, 2013. PMCID: PMC3747125.
Funderburg, N.T., Stubblefield Park, S.R., Sung, H.C., Hardy, G., Clagett, B., Ignatz-Hoover, J., Harding, C.V., Fu, P., Katz, J.A., Lederman, M.M., Levine, A.D. "." Immunology (2013) 140, 87–97; doi: 10.1111/imm.12114. Published online 22 April 2013. PMCID: PMC3809709.
Meisch, J.P., Nishimura, M., Vogel, R.M., Sung, H.C., Bednarchik, B.A., Ghosh, S.K., Fu, P., McCormick, T., Weinberg, A., Levine, A.D."." Inflamm Bowel Dis (2013) 19, 942-953. doi: 10.1097/MIB.0b013e318280b11a. Published online 18 March 2013. PMID: 23511030. NIHMSID 457550. PMCID: PMC3746836.
Das, L.M., Torres-Castillo, M.D.L.A., Gill, T., Levine A.D. "." Mucosal Immunology. (2013) 6, 167–176. doi: 10.1038/mi.2012.60. Epub July 11, 2012; PMCID: PMC3504619
Goodman WA, Young AB, McCormick TS, Cooper KD, Levine A.D. "." J. Immunol. 186:3336-3345 (2011); published ahead of print February 9, 2011, doi:10.4049/jimmunol.1001455; PMID: 21307288; PMC3133678.
Franko, J.L., Levine, A.D. "." J. Leuko. Biol. 85(3): 526-538 (2009); PMCID: .
Das, L., Levine, A.D. "." J. Immunol. 180(3): 1490-1498 (2008).
Etling, M.R., Davies, S., Campbell, M., Redline, R.W., Pingfu Fu, P., Levine, A.D. "." J. Leuko. Biol. 82:311-319 (2007)
Rivera Reyes, B.M., Danese, S., Sans, M., Fiocchi, C., Levine, A.D. "." J. Immunology 175: 2158-2166 (2005).
Schade, A.E, Levine, A.D. "." J Immunol. 172: 5828-5832 (2004).
Sturm, A., Krivacic, K.A., Fiocchi, C., Levine, A.D. "." J. Immunol. 173: 3889-3900 (2004).
Krivacic, K.A., Levine, A.D. "." J. Immunol. 170: 5034-5044 (2003).
Schade, A.E., Levine, A.D. "." Molecular Immunology 40 (8): 531-537 (2003).
Spencer, D.M., Veldman, G.M., Banerjee S., Willis, J., Levine, A.D. "." Gastroenterology 122:94-105 (2002).
Schade, A.E., Levine, A.D. "." J. Immunology 168:2233-2239 (2002).
Jump, R.J., Levine, A.D. "." J. Immunology 168 (12): 6113-6119 (2002).
Pandiyan, P., Younes, S. A., Ribeiro, S. P., Talla, A., McDonald, D., Bhaskaran, N., Levine, A. D., Weinberg, A., and Sekaly, R. P. “.” Front Immunol (2016) 7, 228; doi: 10.3389/fimmu.2016.00228.
Pagano, M.E., Maietti, C.M., Levine, A.D. “.” Am J Drug Alcohol Abuse (2015) 41(3). 230-236; Early Online: 1–7. DOI: 10.3109/00952990.2014.939753.
Klatt, N.R., Harris, L.D., Vinton, C.L., Sung, H., Briant, J.A., Tabb, B., Morcock, D., McGinty, J.W., Lifson, J.D., Lafont, B.A., Martin, M.A., Levine, A.D., Estes, J.D., Brenchley, J.M. (2010). . Mucosal Immunology 3(4): 387–398.