Session Information
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 γδ 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 model, γδNKT cells exacerbated IL-2 plus IL-18 induced lung inflammation via the production of IFN-γ. Thus, to examine whether TCR Vδ1+ 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) In SSc patients with IP, the correlation between proportion of TCR Vδ1+ NKT cells in PBMCs and serum KL-6 levels was analyzed. 3) 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. 4) Cytokine (IFN-γ, TNF-α, IL-4, IL-17) and chemokine (CCL2, CCL3, CCL4, CCL5) secretion assay using TCR Vδ1+ NKT cells from HC and SSc patients was performed. 5) The effect of culture supernatant of TCR Vδ1+ NKT cells on fibroblast proliferation was evaluated.
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. 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. 2) In IP-positive SSc patients, the proportion of TCR Vδ1+ NKT cells correlated negatively with serum KL-6 values (r=-0.464, p<0.05). 3) 192 genes were highly expressed in TCR Vδ1+ NKT cells compared to CD161– Vδ1+ γδT cells. One of 192 genes was CCL3 chemokine associating with SSc and IP. 4) Upregulation of CCL3 and downregulation of IFN-γ production were noted in TCR Vδ1+ NKT cells of IP-positive SSc patients upon TCR stimulation compared with HC (p<0.05). 5) Fibroblast proliferation was promoted with medium supplemented with culture supernatant derived from IP-positive SSc patients (p<0.05), whereas that from HC was not.
Conclusion: TCR Vδ1+ NKT cells might play a regulatory role in the pathogenesis of IP in SSc patients.
Disclosure:
S. Segawa,
None;
D. Goto,
None;
M. Horikoshi,
None;
Y. Kondo,
None;
N. Umeda,
None;
S. Hagiwara,
None;
M. Yokosawa,
None;
T. Hirota,
None;
H. Miki,
None;
H. Tsuboi,
None;
H. Ogishima,
None;
T. Suzuki,
None;
I. Matsumoto,
None;
T. Sumida,
None.
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