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Role for hedgehog pathway in regulating growth and function of invariant NKT cells.

Publication ,  Journal Article
Syn, W-K; Witek, RP; Curbishley, SM; Jung, Y; Choi, SS; Enrich, B; Omenetti, A; Agboola, KM; Fearing, CM; Tilg, H; Adams, DH; Diehl, AM
Published in: Eur J Immunol
July 2009

Lymphocyte accumulation is characteristic of chronic hepatitis, but the mechanisms regulating lymphocyte numbers and their roles in liver disease progression are poorly understood. The Hedgehog (Hh) pathway regulates thymic development and lymphopoeisis during embryogenesis, and is activated in fibrosing liver disease in adults. Our objective was to determine if Hh ligands regulate the viability and phenotype of NKT cells, which comprise a substantial sub-population of resident lymphocytes in healthy adult livers and often accumulate during liver fibrosis. The results demonstrate that a mouse invariant NKT cell line (DN32 iNKT cells), mouse primary liver iNKT cells, and human peripheral blood iNKT cells are all responsive to sonic hedgehog (Shh). In cultured iNKT cells, Shh enhances proliferation, inhibits apoptosis, induces activation, and stimulates expression of the pro-fibrogenic cytokine, IL-13. Livers of transgenic mice with an overly active Hh pathway harbor increased numbers of iNKT cells. iNKT cells also express Shh. These results demonstrate that iNKT cells produce and respond to Hh ligands, and that Hh pathway activation regulates the size and cytokine production of liver iNKT cell populations. Therefore, Hh pathway activation may contribute to the local expansion of pro-fibrogenic iNKT cell populations during certain types of fibrosing liver damage.

Duke Scholars

Published In

Eur J Immunol

DOI

EISSN

1521-4141

Publication Date

July 2009

Volume

39

Issue

7

Start / End Page

1879 / 1892

Location

Germany

Related Subject Headings

  • Suppressor of Cytokine Signaling Proteins
  • Suppressor of Cytokine Signaling 3 Protein
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Cell Surface
  • Patched Receptors
  • Natural Killer T-Cells
  • Mice, Inbred Strains
  • Mice, Inbred C57BL
  • Mice
 

Citation

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Syn, W.-K., Witek, R. P., Curbishley, S. M., Jung, Y., Choi, S. S., Enrich, B., … Diehl, A. M. (2009). Role for hedgehog pathway in regulating growth and function of invariant NKT cells. Eur J Immunol, 39(7), 1879–1892. https://doi.org/10.1002/eji.200838890
Syn, Wing-Kin, Rafal P. Witek, Stuart M. Curbishley, Youngmi Jung, Steve S. Choi, Barbara Enrich, Alessia Omenetti, et al. “Role for hedgehog pathway in regulating growth and function of invariant NKT cells.Eur J Immunol 39, no. 7 (July 2009): 1879–92. https://doi.org/10.1002/eji.200838890.
Syn W-K, Witek RP, Curbishley SM, Jung Y, Choi SS, Enrich B, et al. Role for hedgehog pathway in regulating growth and function of invariant NKT cells. Eur J Immunol. 2009 Jul;39(7):1879–92.
Syn, Wing-Kin, et al. “Role for hedgehog pathway in regulating growth and function of invariant NKT cells.Eur J Immunol, vol. 39, no. 7, July 2009, pp. 1879–92. Pubmed, doi:10.1002/eji.200838890.
Syn W-K, Witek RP, Curbishley SM, Jung Y, Choi SS, Enrich B, Omenetti A, Agboola KM, Fearing CM, Tilg H, Adams DH, Diehl AM. Role for hedgehog pathway in regulating growth and function of invariant NKT cells. Eur J Immunol. 2009 Jul;39(7):1879–1892.
Journal cover image

Published In

Eur J Immunol

DOI

EISSN

1521-4141

Publication Date

July 2009

Volume

39

Issue

7

Start / End Page

1879 / 1892

Location

Germany

Related Subject Headings

  • Suppressor of Cytokine Signaling Proteins
  • Suppressor of Cytokine Signaling 3 Protein
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Cell Surface
  • Patched Receptors
  • Natural Killer T-Cells
  • Mice, Inbred Strains
  • Mice, Inbred C57BL
  • Mice