Physiological contribution of CD44 as a ligand for E-selectin during inflammatory T-cell recruitment

Maria Nácher, Ana Belén Blázquez, Bojing Shao, Adela Matesanz, Colette M. Prophete, M. Cecilia Berin, Paul S. Frenette, Andrés Hidalgo

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Endothelial selectins guide the migration of inflammatory T cells to extralymphoid tissues. Whereas Pselectin glycoprotein ligand-1 (PSGL-1) functions as the exclusive ligand for P-selectin, it acts in coordination with additional glycoproteins to mediate Eselectin binding. CD44 can act as one such ligand in neutrophils, but its contribution in inflammatory T lymphocytes remains unexplored. We have used realtime in vivo imaging of the cremasteric and dermal microcirculations to explore the dynamics of leukocyte recruitment, as well as the physiological contribution of CD44 in a model of Th1-driven inflammation. CD4+ T-cell rolling frequency and kinetics, as well as arrest, were dependent on endothelial selectins and were markedly altered under inflammatory conditions. CD44 extracted from Th1 cells bound to soluble E-selectin in vitro and cooperated with PSGL-1 by controlling rolling velocities and promoting firm arrest. Using several competitive recruitment assays in a delayed-type hypersensitivity model, we show that the combined absence of CD44 and PSGL-1 impairs inflammatory T-cell recruitment beyond that of PSGL-1 alone. Differential expression of leukocyte fucosyltransferases in these cells may account for the differential use of E-selectin ligands relative to neutrophils. Our results identify additional mechanisms by which CD44 modulates the inflammatory response.

Original languageEnglish (US)
Pages (from-to)2437-2446
Number of pages10
JournalAmerican Journal of Pathology
Volume178
Issue number5
DOIs
StatePublished - May 2011

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E-Selectin
Ligands
T-Lymphocytes
Glycoproteins
Selectins
Neutrophils
Leukocytes
Fucosyltransferases
Th1 Cells
P-Selectin
Delayed Hypersensitivity
Microcirculation
Inflammation
Skin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Physiological contribution of CD44 as a ligand for E-selectin during inflammatory T-cell recruitment. / Nácher, Maria; Blázquez, Ana Belén; Shao, Bojing; Matesanz, Adela; Prophete, Colette M.; Berin, M. Cecilia; Frenette, Paul S.; Hidalgo, Andrés.

In: American Journal of Pathology, Vol. 178, No. 5, 05.2011, p. 2437-2446.

Research output: Contribution to journalArticle

Nácher, Maria ; Blázquez, Ana Belén ; Shao, Bojing ; Matesanz, Adela ; Prophete, Colette M. ; Berin, M. Cecilia ; Frenette, Paul S. ; Hidalgo, Andrés. / Physiological contribution of CD44 as a ligand for E-selectin during inflammatory T-cell recruitment. In: American Journal of Pathology. 2011 ; Vol. 178, No. 5. pp. 2437-2446.
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