Role of CD44 in the differentiation of Th1 and Th2 cells: CD44-deficiency enhances the development of Th2 effectors in response to sheep RBC and chicken ovalbumin.
CD4 T cells can be primarily polarized to differentiate into Th1 or Th2 cells. CD44 is a marker of T cell activation and a property of long-lived memory cells and implicated in cell migration, activation, and differentiation. To date, whether CD44 has a role in regulating Th1-Th2 differentiation has not been determined. In this study, we compared Th1 and Th2 responses in wild-type and CD44-deficient mice in response to sheep RBC and chicken OVA, as well as examined Th1-Th2 differentiation in vivo and in vitro from CD44-sufficient and CD44-deficient naive CD4 T cells. We observed that deficiency of CD44 tended to inhibit Th1 while promoting Th2 differentiation. Furthermore, chimeric studies suggested that CD44 expression by CD4 T cells was essential for such Th2 bias. The regulation by CD44 occurred at the transcription level leading to up-regulated GATA3 and down-regulated T-bet expression in activated CD4 T cells. We also noted that CD44-deficiency could modify the state of dendritic cell subsets to induce a Th2-biased development. Results presented in this study demonstrate for the first time that CD44 participates in the regulation of Th1-Th2 differentiation.
Guan
Hongbing
H
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, 29209, USA.
Nagarkatti
Prakash S
PS
Nagarkatti
Mitzi
M
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D002645:Chickens; D015536:Down-Regulation / Q000276:immunology; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000276:immunology*; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D012756:Sheep; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D007074:Immunoglobulin G; D010047:Ovalbumin