T-cell receptor-mediated characteristic signaling pathway of peripheral blood T cells in dermatomyositis and polymyositis

<p>The characteristics of T cell expression in peripheral blood have been previously described in dermatomyositis (DM) and polymyositis (PM); however, their intracellular signaling profiles remain unknown. The purpose of this study was to investigate the T-cell receptor (TCR)-mediated intracellular signaling in peripheral blood T cells in DM and PM. Peripheral blood T cells from 86 patients with DM (<i>n</i> = 57) and PM (<i>n</i> = 29) were used for experimental investigations. T-cell subtypes and TCR-induced phosphorylated zeta-chain-associated protein kinase 70 (pZAP70) were analyzed by flow cytometry. Signal transducer and activator of transcription (STAT) and some inhibitory factors in T cells with TCR stimulation were also investigated by quantitative real-time polymerase chain reaction. T cell counts were significantly lower in DM than in PM. In addition, STAT, forkhead box transcription factor (FoxP3), and pZAP70 expression in CD4⁺ T cells was suppressed in DM, whereas STAT and pZAP70 expression in CD8⁺ T cells was induced in PM. Especially in DM, a positive correlation between CD4⁺ T cell counts and STAT expression was detected. In addition, low CD4⁺ T cell counts as well as reduced STAT expression were prominent in patients with interstitial lung disease. STAT and pZAP70 expression significantly improved after clinical remission in both DM and PM, although expression of FoxP3 remained suppressed. Besides, upregulation of suppressor of cytokine signaling-3 (SOCS3) and downregulation of interleukin 6 signal transducer (IL6ST) in CD4⁺ T cells were observed in both DM and PM; however, no significant improvements were detected after clinical remission. The results of the present study suggested that TCR-mediated signaling may be a key pathway to determine the different characteristics of peripheral blood T cells between DM and PM. In addition, upregulation of SOCS3 and downregulation of IL6ST and FoxP3 in CD4⁺ T cells may cause an imbalance in intracellular signaling, especially in DM, suggesting that further studies are required to identify how the impaired signaling contributes to the development of the disease.</p

Comparison of ET30 and ET60 images.

<p>The FA values for ET60 were significantly higher than those for ET30 in most of the white matter, with slight left hemisphere predominance. These data were overlaid onto the MNI152_T1 template, and the mean FA skeleton is shown in green. The significance level was set at a <i>P</i> value of <0.05 with FWE correction.</p

Representative diffusion-weighted images with the 60 directions encoding scheme.

<p>The images were from the same subject and slice location. The NC60 with forward phase-encoding blips had an artifactual signal pileup around the temporal base of the skull, which was not corrected in EC60, but corrected in ET60. Again, the EC30 with trilinear were blurred, compared with EC30 with spline interpolation.</p

Representative diffusion-weighted images with the 30 directions encoding scheme.

<p>The images were from the same subject and slice location, with forward phase-encoding blips (left panel), and with reversed phase-encoding blips (right panel). NC30 had an artifactual signal pileup around the frontal base of the skull, which was corrected not in EC30 with trilinear or spline but in ET30. The EC30 with trilinear interpolation were blurred, compared with EC30 with spline interpolation.</p

Efficiency of correction schemes acquired with 60 directions diffusion encoding.

<p>Tripled paired group comparisons with TBSS were conducted between NC60 and EC60 with spline interpolation in the upper, NC60 and ET60 in the middle, and EC60 with spline and ET60 in the lower row. The FA values for ET60 were significantly higher than those for NC60 or EC60 in most of the white matter skeleton (blue/lightblue). In contrast, white matter skeleton with significantly higher (blue/lightblue) and lower (red/yellow) FA values for EC60 with spline interpolation than those for NC60 were observed in various areas. These data were overlaid onto the MNI152_T1 template, and the mean FA skeleton is shown in green. The significance level was set at a <i>P</i> value of <0.05 with FWE correction.</p