FcγRIII engagement provides activating signals to NKT cells in antibody-induced joint inflammation
Hye Young Kim, … , Sanghee Kim, Doo Hyun Chung
Hye Young Kim, … , Sanghee Kim, Doo Hyun Chung
Published September 1, 2006
Citation Information: J Clin Invest. 2006;116(9):2484-2492. https://doi.org/10.1172/JCI27219.
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Research Article Autoimmunity

FcγRIII engagement provides activating signals to NKT cells in antibody-induced joint inflammation

Abstract

NKT cells promote antibody-induced arthritis, but the mechanism by which NKT cells are activated in this model remains unclear. It has been proposed that Fcγ receptor (FcγR) contributes to NKT cell activation in antibody-induced arthritis. To address this issue, we explored the functions of FcγR on NKT cells in antibody-induced arthritis. RT-PCR and flow cytometric analysis demonstrated that NKT cells constitutively express surface FcγRIII but not FcγRI, -II, or -IV. FcγRIII engagement by aggregated IgG on NKT cells enhanced CD25 and CD69 expression, whereas FcγR–/– mouse NKT cells did not enhance activation. FcγRIII engagement on NKT cells enhanced the production of IL-4, IL-10, IL-13, and IFN-γ, whereas FcγR-deficient NKT cells did not alter the production of these cytokines after aggregated IgG treatment. However, FcγR-deficient NKT cells were functionally intact in terms of TCR-induced activation. Moreover, adoptive transfer of FcγR-deficient NKT cells could not restore inflammation or TGF-β production in the joint tissues of CD1d–/– mice, whereas adoptive transfer of wild-type NKT cells induced arthritis and reduced TGF-β production in joint tissues. We conclude that FcγRIII engagement by IgG in joint tissues provides activating signals to NKT cells in antibody-induced arthritis.

Authors

Hye Young Kim, Sanghee Kim, Doo Hyun Chung

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Figure 1

NKT cells constitutively express surface FcγRIII.

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NKT cells constitutively express surface FcγRIII. (A) FcγRI, -II, -III, ...
(A) FcγRI, -II, -III, and -IV expression on sorted NK1.1+TCRβ+ NKT cells, NK1.1+TCRβ– NK cells, and splenocytes (SPC) freshly isolated from B6 mice was analyzed by RT-PCR. (B) FcγRII and FcγRIII expression was analyzed on gated NKT cells, NK cells, NK1.1–TCRβ+ T cells, and B220+ B cells using 2.4G2 or Ly17.2 mAb. Cells were also preincubated with Ly17.2 mAb and stained with 2.4G2. As a negative control, cells were stained with isotype-matched IgG for 2.4G2 or Ly17.2 mAbs (open histogram). Numbers indicate mean fluorescence intensity (MFI) ± SD. (C) The expression of CD4/CD8 or Vα14+TCR was analyzed on gated TCRβ+2.4G2+ liver MNCs using anti-CD4 and CD8 mAb or α-GalCer/CD1d dimer. Numbers indicate percent of cells ± SD. (D) Liver MNCs were freshly isolated from B6 mice and cultured with α-GalCer (220 ng/ml) or aggregated IgG (Agg IgG; 10 μg/ml) for 24 hours. FcγRIII expression was analyzed on gated NKT, NK, and T cells. Open histograms represent negative controls, which were stained with anti-NK1.1 and -TCRβ mAbs and isotype-matched IgG for 2.4G2. Numbers indicate MFI ± SD. Results are representative of 3 independent experiments. *P < 0.05.