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 3

Adoptive transfer of Fc γR–/– mouse NKT cells into CD1d–/– mice does not restore joint inflammation in a K/BxN serum transfer model.

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Adoptive transfer of Fc γR–/– ...
(A) Sorted NKT cells (3 × 105 cells/mouse) from B6 or FcγR–/– mice were adoptively transferred into CD1d–/– mice (B6 NKT transfer or FcγR–/– NKT transfer, respectively) 1 day before the K/BxN serum transfer (n = 5 per group). Clinical scores and ankle thickness were monitored in B6 and CD1d–/– mice as well as in CD1d–/– mice administered NKT cells of B6 or FcγR–/– mice after injecting K/BxN serum. (B) Histological and gross examination of the ankle joints of B6 and CD1d–/– mice as well as CD1d–/– mice administered B6 or FcγR–/– mouse NKT cells 5 days after serum transfer. Original magnification, ×200 (middle panels); ×1,000 (bottom panels). Arrows in bottom panels indicate neutrophils in the joint tissues. (C) RT-PCR and real-time PCR were used to determine Vα14Jα218 TCR mRNA levels in the ankle joint tissues of B6 and CD1d–/– mice as well as CD1d–/– mice administered B6 or FcγR–/– mouse NKT cells. RT-PCR and real-time PCR were performed 10 days after K/BxN serum transfer. (D) TGF-β1, IL-4, and IFN-γ mRNA levels were measured by real-time PCR in the joint tissues and spleens of B6 mice, CD1d–/– mice, and CD1d–/– mice administered B6 or FcγR–/– mouse NKT cells 10 days after K/BxN serum transfer. Results are representative of 3 independent experiments. *P < 0.05; **P < 0.01.