Specific Overexpression of FPR2 (FPRL-1) on Th1 Cells in GPI-Induced Arthritis and Patients with Rheumatoid Arthritis

Yuki Tanaka¹, Isao Matsumoto², Asuka Inoue³, Naoto Umeda⁴, Chinatsu Takai⁵, Yuko Kurashima⁶, Hoshimi Kawaguchi⁶ and Takayuki Sumida⁷, ¹Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba city, Ibaraki, Japan, ²Department of Interenal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan, ³Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, University of Tsukuba, Tsukuba city, Ibaraki, Japan, ⁴Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba City, Japan, ⁵University of Tsukuba, Ibaraki, Japan, ⁶University of Tsukuba, Tsukuba, Japan, ⁷Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: animal models and rheumatoid arthritis (RA), T cells

Session Information

Title: Rheumatoid Arthritis - Animal Models

Session Type: Abstract Submissions (ACR)

【Background/Purpose 】

CD4⁺T cell are critical to the pathogenesis of rheumatoid arthritis (RA). In glucose-6-phosphate isomerase (GPI) induced-arthritis (GIA), Th1 and Th17 cells are indispensable for both the induction and the effector phase. We recently identified the highly expression of formyl peptide receptor 2 (FPR2) in splenic CD4⁺T cells from GIA mice by DNA microarray. The FPR2 (human homologue: FPRL-1) is a G-protein coupled receptor showing pro- and anti-inflammatory effect. To clarify the function of FPR2 in CD4+ T cells in the generation of arthritis, we investigated the expression of FPR2 in GIA and FPRL-1 in patients with RA.

【Methods 】

(1) To confirm the results of DNA microarray, we analyzed the fluctuated expression of FPR2 mRNA on CD4⁺T cells in GIA (day0, day 7: induction phase, day 14: effector phase, day 28: contraction phase) by real-time PCR.

(2) To determine the Th subsets expressing FPR2, we sorted FPR2⁺ or FPR2^–CD4⁺T cells from lymph nodes of GIA (on day7), and the mRNA expression of various markers on CD4⁺T cell subsets (Th1, 2, 17, Tfh and Treg) was examined.

(3) We analyzed the expression of FPR2 on Th1 or Th17 cells in the polarized condition in vitro.

(4) In human, we analyzed the expression of FPRL-1 mRNA on peripheral blood mononuclear cells (PBMC) and CD4⁺T cells from healthy subjects (HS), patients with Sjogren’s syndrome (SS), and RA patients.

(5) We assessed the expression of FPRL-1 on human Th1 cells in the polarized condition in vitro.

【Results 】

(1) The FPR2 mRNA was significantly highly expressed on CD4⁺T cells in GIA on day7 (p<0.05).

(2) The T-bet and IFNγ were higher expressed on FPR2⁺CD4⁺T cells than those on FPR2^–CD4⁺T cells, whereas each marker for Th2, Th17, Tfh and Treg cells were not.

(3) The expression of FPR2 was frequently detected on Th1 polarized cells, but not on Th17 polarized cells.

(4) The expression of FPRL-1 on PBMC and CD4⁺ cells was significantly higher in RA compared with HS and SS (p<0.05).

(5) FPRL-1 expression was significantly increased on human Th1 polarized cells.

【Conclusion 】

We identified that FPR2⁺T cells showed Th1 phenotype in mice and FPRL-1 was highly detected on CD4⁺T cells in patients with RA. Th1 polarized cells in mice and humans also expressed FPR2 and FPRL-1, respectively, suggesting FPR2⁺(FPRL-1⁺) T cells might play a crucial role in the pathogenesis of RA.

Disclosure:

Y. Tanaka,
None;

I. Matsumoto,
None;

A. Inoue,
None;

N. Umeda,
None;

C. Takai,
None;

Y. Kurashima,
None;

H. Kawaguchi,
None;

T. Sumida,
None.

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