CD43 dependent mechanisms of Th17 cell recruitment to sites of inflammation and autoimmune reactions
Velázquez Planas, Francisco.
IL17 producing T helper lymphocytes (Th17 cells) are often recruited at sites of tissue
inflammation and participate in cell-mediated inflammatory reactions that involve
interactions with the vascular endothelium. These interactions are quantitatively
different from the Th1 T cell subset, and are highly dependent on E-selectin. T cell
expressed E-selectin ligands were described before ... read morethe existence of Th17 cells emerged,
thus, their contribution to Th17 recruitment is unclear. One such ligand is
syaloglycoprotein CD43, a protein with other pleiotropic functions but with unknown
roles in Th17 cells. Chapter 3.1 of the present thesis dissertation tests the hypothesis
that Th17 cells use specific E-selectin ligands that differ from other T cell subsets,
and identifies CD43 as a major Th17 cell expressed E-selectin ligand in vitro and in
vivo. We combine real time videomicroscopy and adhesion experiments under flow
conditions in vitro, and the air pouch model of leukocyte recruitment as well as
intravital microscopy of the inflamed cremaster muscle in vivo. In Chapter 3.2, we test
the hypothesis that CD43 regulates antigen specific Th17 cell recruitment to sites of
autoimmune reactions, using the mouse model of Experimental Autoimmune Encephalomyelitis
(EAE). We find that CD43 regulates Th17 cell recruitment to the spinal cord in an
E-selectin independent way, and hypothesize that CD43 regulates Th17 cell adhesion to
ICAM-1. We present evidence that CD43 regulates Th17 cell adhesion and apical migration
on ICAM-1, as well as ICAM-1 dependent transmigration in vitro. Lastly, in Chapter 3.3,
we test the hypothesis that CD43 contributes to pathological cardiac remodeling and
heart failure (HF), using the thoracic aortic constriction model (TAC) in which both
E-selectin and ICAM-1 are upregulated in the heart. We demonstrate for the first time
that CD43 contributes to T cell and monocyte recruitment to the heart, cardiac fibrosis
and systolic dysfunction. In summary, we report several new roles for the
sialoglycoprotein CD43, some of which are specific of Th17 cells, and others more broad
in the context of heart inflammation in vivo. Our results identify new CD43 regulated
pathways involved in Th17 cell recruitment and in inflammation associated with cardiac
Thesis (Ph.D.)--Tufts University, 2017.
Submitted to the Dept. of Immunology.
Advisor: Pilar Alcaide.
Committee: Mercio Perrin, Honorine Ward, and Thereza Imanishi-Kari.
Keyword: Immunology.read less