Trafficking of T cells is crucial for every phase of T cell function from the initiation of the immune response to effector function at the site of inflammation. T cells move into the lymph node, where they move through the tissue to maximize the chances of encountering an antigen bearing dendritic cell. Once activated, T cells then migrate to inflammatory sites to perform effector functions to clear infection. T cell migration has also been shown to be an important mediator of disease states including cardiovascular disease, diabetes, and cancer. While the process of T cell migration is critical to immune function, relatively little is known about the precise behavior of T cells in the lymph node and the specific molecules that control T cell migration.
The Cannon laboratory is focused on defining and understanding the fundamental mechanisms that control T cell migration to and within lymph nodes. We identified the glycoprotein CD43, PKCθ, as well as cytoskeletal regulatory proteins Ezrin-Radixin-Moesin (ERM) as regulators of T cell migration. We are also analyzing precisely how T cells move within lymph nodes.
We are using cutting edge 2 photon microscopy imaging techniques to visualize T cell movement in live tissue. In addition, we use a combination of flow cytometry, confocal microscopy, and standard biochemistry to understand the effect of signaling molecules on T cell trafficking. We are also beginning use live tissue imaging to visualize T cell movement in mouse lung infected with flu.
Interestingly, the same signals that drive T cell migration are shared by T-ALL leukemia cells for metastasis. In collaboration with pediatric oncologists at UNM, we are also studying whether the same pathways that govern normal T cell migration may also play a role in leukemia cell metastasis. Again, using mouse models, we can visualize human leukemic cells in a mouse model to study what molecules might provide targets for leukemia migration.
Selected PublicationsLink to PubMed
Oruganti SR, Torres DJ, Krebsbach S, Asperti-Boursin F, Winters J, Matlawska-Wasowska K, Winter SS, Halsey C, Cannon JL*. CARMA1 is a novel regulator of T-ALL disease and leukemic cell migration to the CNS. Leukemia. 2016 Oct 21.
Torres DJ, Cannon JL, Ricoy UM, Johnson C. Self-Contained Statistical Analysis of Gene Sets. PLoS One. 2016 Oct 6;11(10):e0163918
Fricke GM, Letendre KA, Moses ME, Cannon JL*. Persistence and Adaptation in Immunity: T Cells Balance the Extent and Thoroughness of Search. PLoS Comput Biol. 2016 Mar 18; 12(3):e1004818. PMCID: PMC4798282.
Carroll-Portillo A, Cannon JL, te Riet J, Holmes A, Kawakami Y, Kawakami T, Cambi A, Lidke DS. Mast cells and dendritic cells form synapses that facilitate antigen transfer for T cell activation. J Cell Biol. 2015 Aug 31;210(5):851-64. PMCID: PMC4555818.
Letendre K, Donnadieu E, Moses ME, Cannon JL*. Bringing statistics up to speed with data in analysis of lymphocyte motility. PLoS One. 2015 May 14;10(5):e0126333. PMCID: PMC4431811.
Wan G, Pehlke C, Pepermans R, Cannon JL, Lidke D, Rajput A. The H1047R point mutation in p110 alpha changes the morphology of human colon NCT116 cancer cells. Cell Death Discov. 2015 Oct 19;1:15044. PMCID: PMC4979441.
Cannon J.L.*, Asperti-Boursin, F., Letendre, K., Brown, I.K., Korzekwa, K.E., Blaine, K. M. Oruganti, S.R., Sperling, A.I., Moses, M.E. PKCθ regulates T cell motility via Ezrin-Radixin-Moesin localization to the uropod. PLOS One. 2013 Nov 8;8(11):e78940. PMID: 24250818 PMCID: PMC3826749 *corresponding author.
Jesse Williams, Douglas Yau, Nan Sethakorn, Jacob Kach, Eleanor Reed, Tamson Moore, Judy L. Cannon, Xiaohua Jin, Heming Xing, Anthony Muslin, Anne Sperling, and Nickolai Dulin. RGS3 controls T lymphocyte migration in a model of Th2-mediated airway inflammation. Am J Physiol Lung Cell Mol Physiol. 2013 Nov;305(10):L693-701. PMID: 24077945 PMCID: PMC3840273.
Qiang Wu, Elizabeth Berry, Tiffany Lu, Bryan S. Clay, Tamson V. Moore, Caroline M. Ferreira, Jesse W. Williams, Jasmine Moreno, Judy L. Cannon, Anne I. Sperling, and Rebecca A. Shilling. ICOS-expressing Tregs Promote Resolution of CD8-mediated Lung Injury. PLoS One. 2013;8(8):e72955. PMID: 23967339 PMCID: PMC3742557
Zhou HF, Yan H, Cannon JL, Springer LE, Green JM, Pham CT. CD43-Mediated IFN-γ Production by CD8+ T Cells Promotes Abdominal Aortic Aneurysm in Mice. J Immunol. 2013 May 15;190(10):5078-85. PMID: 23585675
Cannon, J.L.#, Mody, P.D., Blaine, K.M., Nelson, A.D., Sayles, L., Moore, T.V., Clay, B.S., Bandukwala, H.S., Dulin, N.O., Shilling, R.A., Sperling, A.I. CD43 interaction with ERM proteins regulates T cell trafficking and CD43 phosphorylation. Molecular Biology of the Cell, 2011. Apr;22(7):954-63. #corresponding author PMID: 21289089
Moore TV, Clay BS, Ferreira CM, Williams JW, Rogozinska M, Cannon JL, Shilling RA, Marzo AL, Sperling AI. Protective effector memory CD4 T cells depend on ICOS for survival. PLoS One. 2011 Feb 18;6(2):e16529. PMID: 2136474
Driessens, G., Zheng, Y., Locke, F., Cannon, J.L., Gounari, F., Gajewski, T.F. 2011. β-catenin inhibits T cell activation by selective interference with LAT-PLC-γ1 phosphorylation. Journal of Immunology, Jan 15;186(2):784-90. PMID: 21149602
Shaffer MH, Huang Y, Corbo E, Wu GF, Velez M, Choi JK, Saotome I, Cannon JL, McClatchey AI, Sperling AI, Maltzman JS, Oliver PM, Bhandoola A, Laufer TM, Burkhardt JK. 2010. Ezrin is highly expressed in early thymocytes, but dispensable for T cell development in mice. PLoS One. 2010 Aug 27;5(8). pii: e12404. PMID: 20806059
Clay BS, Shilling RA, Bandukwala HS, Moore TV, Cannon JL, Welcher AA, Weinstock JV, Sperling AI. 2009. Inducible costimulator expression regulates the magnitude of Th2-mediated airway inflammation by regulating the number of Th2 cells. PLoS One. Nov 4;4(11):e7525. PMID: 19888475
Shilling, R.A., Clay, B.S., Moore, T.V., Berry, E., Tesciuba, A.G., Bandukwala, H.S., Tong, J., Weinstock, J.V., Flavell, R.A., Horan, T., Yoshinaga S.K., Welcher, A.A., Cannon, J.L., Sperling, A.I. 2009. CD28 and ICOS play complementary non-overlapping roles in the development of Th2 immunity in vivo. Cellular Immunology, 2009;259(2):177-84. PMID: 19646680
Cannon, J.L.*#, Collins A. *, Balachandran D., Henriksen, K.J., Clay, B.S., Mody, P.D., Smith, C.E., Tong J., Miller S.D., Sperling A.I. 2008. CD43 regulates Th2 differentiation and inflammation. Journal of Immunology, 180: 7385-7393. *co-first authorship, #corresponding author. PMID: 18490738
Mody, P.D.*, Cannon, J.L.*, Bandukwala, H.S., Blaine, K.M., Schilling, A.B., Swier K., Sperling, A.I. 2007. Signaling through CD43 is required for CD4 T cell trafficking. Blood, Oct 15;110(8):2974-82. *co-first authorship. PMID: 17638845
Bandukwala, H.S., B.S. Clay, J. Tong, P.D. Mody, J.L. Cannon, R.A. Shilling, J.S. Verbeek, J.V. Weinstock, J. Solway, and A.I. Sperling. 2006. Signaling through FcγRIII is required for optimal Th2 responses and Th2-mediated airway inflammation. Journal of Experimental Medicine 204(8):1875-89. PMID: 17664287
Cannon, J.L., Burkhardt, J.K. Differential roles for WASP in actin regulation and IL2 production. 2004. Journal of Immunology 173(3):1658-62. PMID: 15265894
Zeng, R., Cannon, J.L., Abraham, R.T., Way, M., Billadeau, D.D., Bubeck-Wardenberg, J., Burkhardt, J.K. 2003. SLP-76 coordinates Nck-dependent Wiskott-Aldrich syndrome protein recruitment with Vav-1/Cdc42-dependent Wiskott-Aldrich syndrome protein activation at the T cell-APC contact site. Journal of Immunology 171(3):1360-8. PMID: 12874226
Cannon, J.L., C. Case, G. Bosco, A. Seth, M. McGavin, K.A. Siminovitch, M.K. Rosen, and J.K. Burkhardt. 2001. WASP recruitment to the T cell-APC contact site occurs independently of Cdc42 Activation. Immunity 15:249-259. PMID: 11520460
Allenspach, E.J., P. Cullinan, J. Tong, Q. Tang, A.G. Tesciuba, J.L. Cannon, S.M. Takahashi, R. Morgan, J.K. Burkhardt, and A.I. Sperling. 2001. ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse. Immunity, 15:739-750. PMID: 11728336
J.L. Cannon, J. Miller and J.K. Burkhardt. 1999. TCR, LFA-1 and CD28 play unique and complementary roles in T cell cytoskeletal reorganization. Journal of Immunology 162:1367-1375. PMID: 9973391Sedwick, C.E., M.M. Morgan, L. Jusino, J.L. Cannon, J. Miller and J.K. Burkhardt. 1999. TCR, LFA-1 and CD28 play unique and complementary roles in T cell cytoskeletal reorganization. Journal of Immunology 162:1367-1375. PMID: 9973391