Timothy DenningFaculty Professor Institute for Biomedical Sciences
Ph.D. Microbiology & Immunology, University of Texas Medical Branch at Galveston 2002
Timothy Denning, Distinguished University Professor at Georgia State University, specializes in research on how antigen presenting cells regulate adaptive immune responses at mucosal surfaces. In particular, he is interested in how intestinal macrophages and dendritic cells control CD4+ T cell differentiation and function in the intestine during homeostasis and inflammatory conditions. The research has applications for inflammatory bowel disease (IBD), a chronic, relapsing inflammatory disorder of the digestive tract.
Denning earned his Ph.D. in Microbiology & Immunology from University of Texas Medical Branch at Galveston in Texas and completed his postdoctoral training at La Jolla Institute for Allergy & Immunology and Emory University.
Regulation of Innate and Adaptive Immune Responses at Mucosal Surfaces
Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the digestive tract. The etiology of IBD is unclear, yet aberrant innate and adaptive immune responses directed towards the microbiota are believed to underlie disease pathogenesis and progression. My laboratory is focused on understanding how antigen presenting cells regulate adaptive immune responses at mucosal surfaces. In particular, we are interested in how intestinal macrophages and dendritic cells control CD4+ T cell differentiation and function in the intestine during homeostasis and inflammatory conditions. Using experimental models of IBD combined with multicolor flow cytometry and high-speed cell sorting, we have begun defining the phenotype and functions of murine and human intestinal macrophage and dendritic cell subsets and how they influence tissue homeostasis, damage and repair.
- Denning T.L., Parkos C.A. Neutrophils enlist IL-22 to restore order in the gut. Proc Natl Acad Sci. 2013 Jul 30.,
- Cebula A., Seweryn M., Rempala G.A., Pabla S.S., McIndoe R.A., Denning T.L., Bry L., Kraj P., Kisielow P., Ignatowicz L. Thymus-derived regulatory T cells contribute to tolerance to commensal microbiota. Nature. 2013 May 9;497(7448):258-62.
- Khounlotham, M., Kim, W., Peatman, E., Nava, P., Medina-Contreras, O., Addis, C., Koch, S., Fournier, B., Nusrat, A., *Denning, T.L. and Parkos C.A. Compromised intestinal epithelial barrier induces adaptive immune compensation that protects from colitis. Immunity. 2012 Sep 21;37(3):563-73. (*co-corresponding author)
- Geem, D., Medina-Contreras, O., Kim, W., Huang, C., and Denning, T.L.. Isolation and characterization of dendritic cells and macrophages from the mouse intestine. J. Vis. Exp. 2012 May 21;(63):e4040.
- Medina-Contreras, O., Geem, D., Laur, O., Williams, I.R., Lira, S.A., Nusrat, A., Parkos, C.A. and Denning, T.L.. CX3CR1 regulates intestinal macrophage homeostasis, bacterial translocation and colitogenic TH17 responses in mice. J. Clin. Invest. 2011 Dec;121(12): 4787-95.
- Denning T.L.*, Norris B.A., Medina-Contreras O, Manicassamy S, Geem D, Madan R, Karp C.L., Pulendran B. Functional Specializations of Intestinal Dendritic Cell and Macrophage Subsets That Control Th17 and Regulatory T Cell Responses Are Dependent on the T Cell/APC Ratio, Source of Mouse Strain, and Regional Localization. J Immunol. 2011 Jul 15;187(2):733-47. (*co-corresponding author)
- Denning, T.L. and Sitaraman, S.V. Segmented filamentous bacteria shape intestinal immunity. Gastroenterology. 2010. Jul; 139.(1):351-3.
- Manicassamy, S., Ravindran, R., Deng, J., Oluoch, H., Denning, T.L., Kasturi, S.P., Rosenthal, K.M., Evavold, B.D., Pulendran, B. Toll-like receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity. Nat Med. 2009 Apr;15(4):401-9.
- Denning, T.L. and Sitaraman, S.V. Adenosine Triphosphate Energizes Intestinal T(H)17 cells. Gastroenterology. 2009. Mar;136(3):1107-9.
- Pulendran, B., Tang, H., and Denning, T.L. Division of labor, plasticity, and crosstalk between dendritic cell subsets. Curr Opin Immunol. 2008 Feb;20(1):61-7.
- Denning, T.L., Wang, Y., Patel, S.R., Williams, I.R., and Pulendran, B. Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses. Nat Immunol. 2007 Oct;8(10):1086-94.
- Denning, T.L., Granger, S., Mucida, D., Graddy, R., Leclercq, G., Zhang, W., Honey, K., Rasmussen, J., Cheroutre, H., Rudensky, A.Y., and Kronenberg, M. Mouse TCRab+ CD8aa intraepithelial lymphocytes express genes that down regulate their antigen reactivity and suppress immune responses. J Immunol. 2007. Apr 1;178(7):4230-9.
- Zhu M, Koonpaew S, Liu Y, Shen S, Denning T., Dzhagalov I, Rhee I, Zhang W. Negative regulation of T cell activation and autoimmunity by the transmembrane adaptor protein LAB. Immunity. 2006 Nov;25(5):757-68.
- Agrawal A, Dillon S, Denning T.L., Pulendran B. ERK1-/- mice exhibit Th1 cell polarization and increased susceptibility to experimental autoimmune encephalomyelitis. J Immunol. 2006 May 15;176(10):5788-96.
- Dillon S, Agrawal S, Banerjee K, Letterio J, Denning T.L., Oswald-Richter K, Kasprowicz DJ, Kellar K, Pare J, van Dyke T, Ziegler S, Unutmaz D, Pulendran B. Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance. J Clin Invest. 2006 Apr;116(4):916-2.
- Denning T.L., Kim G, and Kronenberg M. CD4+CD25+ T cells impaired for intestinal homing can prevent colitis. J Immunol (Cutting Edge). 2005 Jun 15;174(12):7487-91.
- Denning, T.L., Qi, H., Konig, R., Scott, K.G., Naganuma, M., Ernst P.B. CD4+ Th cells resembling regulatory T cells that inhibit chronic colitis differentiate in the absence of interactions between CD4 and class II MHC. J Immunol. 2003 Sep 1;171(5):2279-86.
- Denning, T.L., Takaishi, H., Crowe, S.E., Boldogh, I., Jevnikar, T., and Ernst, P.B. Oxidative stress induces the expression of Fas and Fas ligand and apoptosis in murine intestinal epithelial cells. Free Rad Biol and Med. 33(12); 1641-1650. 2002
- Denning, T.L., Campbell, N., Song, F., Garofalo, R., Rennick, D., Moore, K., Klimpel, G., Reyes, V.E., and Ernst, P.B. Expression and function of IL-10 receptors on murine intestinal epithelial cells. Int. Immunol. 12(2): 133-139. 2000.