Session Information
Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud’s – Pathogenesis, Animal Models and Genetics
Session Type: Abstract Submissions (ACR)
Background/Purpose: Interstitial pneumonia (IP) is one of the critical complications in patients with several autoimmune diseases. However, the exact mechanism of IP remains elusive. Recently, the pathological role of gd T cells was reported in several IP mice models. Previous our data showed that IP in Interleukin (IL)-2 plus IL-18 induced mice was similar to human IP. In this mice, γδNKT cells exacerbated IL-2 plus IL-18 induced lung inflammation via the production of IFN-γ. Thus, to examine whether Vd1+ NKT cells play a crucial role, we carried out the number and function of TCR Vδ1+NKT cells in systemic sclerosis patients with IP.
Methods: 1) PBMCs were isolated from healthy controls (HC, n=22) and patients with rheumatoid arthritis (RA, n=17), systemic sclerosis (SSc, n=35), and polymyositis/dermatomyositis (PM/DM, n=14). We examined the proportion of TCR Vδ1+NKT cells in PBMCs by flow cytometry (FCM). 2) We examined the proportion of TCR Vδ1+NKT cells in patients with autoimmune disease plus IP. 3) We analyzed the correlation between the proportion of TCR Vδ1+NKT cells in PBMCs and serum KL-6 values. 4) CD161– Vδ1+ γδT and CD161+ Vδ1+ γδT cells (TCR Vδ1+NKT cells) in PBMCs were sorted out from HC (n=3). We performed GeneChip analysis using those two cell populations.
Results: 1) The proportion of TCR Vδ1+NKT cells in PBMCs from SSc patients (mean±SEM, 0.55±0.13%) was significantly higher than that of HC (0.23±0.09%, p<0.05), whereas RA (0.38±0.12%) and PM/DM patients (0.23±0.11%) were not. 2) In SSc patients, the proportion of TCR Vδ1+NKT cells in PBMCs from IP-negative subjects (1.03±0.32%) was significantly higher than that of IP-positive subjects (0.28±0.07%, p<0.05). In RA and PM/DM patients, there was no difference between IP-negative and IP-positive subjects. 3) In IP-positive SSc patients, results showed a negative correlation between serum KL-6 values and the proportion of TCR Vδ1+ NKT cells (r=-0.464, p<0.05). In IP-positive PM/DM patients, there were no any correlations. 4) We found highly expressed 192 genes in TCR Vδ1+ NKT cells compared to CD161– Vδ1+ γδT cells. One of 192 genes was CCL3 chemokine associating with SSc and IP. Exactly, the CCL3 mRNA was significantly increased in TCR Vδ1+NKT from SSc patients by real time PCR methods (p<0.05).
Conclusion: TCR Vδ1+ NKT cells might play a crucial role in the generation of IP in patients with SSc.
Disclosure:
S. Segawa,
None;
D. Goto,
None;
M. Horikoshi,
None;
S. Hagiwara,
None;
N. Umeda,
None;
H. Ogishima,
None;
Y. Kondo,
None;
H. Tsuboi,
None;
M. Sugihara,
None;
T. Hayashi,
None;
Y. Chino,
None;
I. Matsumoto,
None;
T. Sumida,
None.
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