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 migrate 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 specific molecules that control T cell migration. Understanding the molecular mechanisms that regulate T cell movement can provide insight into a fundamental T cell function and may lead to novel therapeutic targets to modulate the immune response and disease states.
The Cannon laboratory is focused on defining and understanding the
molecular 
mechanisms that control T cell
migration to and within lymph nodes. Several molecules have been
established to play a key role in T cell migration to lymph nodes,
including CD62L, CCR7, and LFA-1. We identified the glycoprotein CD43
and its associated cytoskeletal regulatory proteins
Ezrin-Radixin-Moesin (ERM) as regulators of T cell migration. Using
these known molecules as a starting point, we will map the molecular
pathways that lead from signaling at the cell surface to intracellular
molecules that work together to control T cell migration.
To define the action of novel molecular players, we will use cutting edge imaging techniques to visualize the effect of individual signaling molecules on T cell movement in living animals. We will use confocal microscopy to detect the localization of specific molecules in migrating T cells (see picture 2). We will also use 2-photon microscopy to see the movement of T cells in living tissue from mice (see picture 1). Together with biochemical assays and in vivo migration experiments using mouse models, we will determine how individual molecules regulate T cell migration.
My Pathology Department web page is here.
Selected Publications
Link to PubMed
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.
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.
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.
Cannon, J.L., Burkhardt, J.K. Differential roles for
WASP in actin regulation and IL2 production. 2004. Journal of
Immunology 173(3):1658-62.
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.
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.
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.
