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TREM-2 mediated signaling induces antigen uptake and retention in mature myeloid dendritic cells.

Publication ,  Journal Article
Radhakrishnan, S; Arneson, LN; Upshaw, JL; Howe, CL; Felts, SJ; Colonna, M; Leibson, PJ; Rodriguez, M; Pease, LR
Published in: J Immunol
December 1, 2008

Myeloid dendritic cells (mDC) activated with a B7-DC-specific cross-linking IgM Ab (B7-DC XAb) take up and retain Ag and interact with T cell compartments to affect a number of biologic changes that together cause strong antitumor responses and blockade of inflammatory airway disease in animal models. The molecular events mediating the initial responses in mDC remain unclear. In this study we show that B7-DC XAb caused rapid phosphorylation of the adaptor protein DAP12 and intracellular kinases Syk and phospholipase C-gamma1. Pretreatment of mDC with the Syk inhibitor piceatannol blocked B7-DC XAb-induced Ag uptake with a concomitant loss of tumor protection in mice. Vaccination with tumor lysate-pulsed wild-type B7-DC XAb-activated mDC, but not TREM-2 knockout XAb-activated mDC, protected mice from lethal melanoma challenge. Multimolecular caps appeared within minutes of B7-DC XAb binding to either human or mouse mDC, and FRET analysis showed that class II, CD80, CD86, and TREM-2 are recruited in tight association on the cell surface. When TREM-2 expression was reduced in wild-type mDC using short hairpin RNA or by using mDC from TREM-2 knockout mice, in vitro DC failed to take up Ag after B7-DC XAb stimulation. These results directly link TREM-2 signaling with one change in the mDC phenotype that occurs in response to this unique Ab. The parallel signaling events observed in both human and mouse mDC support the hypothesis that B7-DC cross-linking may be useful as a therapeutic immune modulator in human patients.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

December 1, 2008

Volume

181

Issue

11

Start / End Page

7863 / 7872

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Syk Kinase
  • Stilbenes
  • Signal Transduction
  • Respiration Disorders
  • Receptors, Immunologic
  • Protein-Tyrosine Kinases
  • Phosphorylation
  • Phospholipase C gamma
  • Neoplasms, Experimental
 

Citation

APA
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MLA
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Radhakrishnan, S., Arneson, L. N., Upshaw, J. L., Howe, C. L., Felts, S. J., Colonna, M., … Pease, L. R. (2008). TREM-2 mediated signaling induces antigen uptake and retention in mature myeloid dendritic cells. J Immunol, 181(11), 7863–7872. https://doi.org/10.4049/jimmunol.181.11.7863
Radhakrishnan, Suresh, Laura N. Arneson, Jadee L. Upshaw, Charles L. Howe, Sara J. Felts, Marco Colonna, Paul J. Leibson, Moses Rodriguez, and Larry R. Pease. “TREM-2 mediated signaling induces antigen uptake and retention in mature myeloid dendritic cells.J Immunol 181, no. 11 (December 1, 2008): 7863–72. https://doi.org/10.4049/jimmunol.181.11.7863.
Radhakrishnan S, Arneson LN, Upshaw JL, Howe CL, Felts SJ, Colonna M, et al. TREM-2 mediated signaling induces antigen uptake and retention in mature myeloid dendritic cells. J Immunol. 2008 Dec 1;181(11):7863–72.
Radhakrishnan, Suresh, et al. “TREM-2 mediated signaling induces antigen uptake and retention in mature myeloid dendritic cells.J Immunol, vol. 181, no. 11, Dec. 2008, pp. 7863–72. Pubmed, doi:10.4049/jimmunol.181.11.7863.
Radhakrishnan S, Arneson LN, Upshaw JL, Howe CL, Felts SJ, Colonna M, Leibson PJ, Rodriguez M, Pease LR. TREM-2 mediated signaling induces antigen uptake and retention in mature myeloid dendritic cells. J Immunol. 2008 Dec 1;181(11):7863–7872.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

December 1, 2008

Volume

181

Issue

11

Start / End Page

7863 / 7872

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Syk Kinase
  • Stilbenes
  • Signal Transduction
  • Respiration Disorders
  • Receptors, Immunologic
  • Protein-Tyrosine Kinases
  • Phosphorylation
  • Phospholipase C gamma
  • Neoplasms, Experimental