School of Biotechnology, Kalinga Institute of Industrial Technology, Bhubaneswar, Odisha, India.
Department of Rheumatology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India.
Sci Rep. 2017 Apr 19;7(1):933. doi: 10.1038/s41598-017-01033-7.
Aberrant immune responses characterize autoimmune disorders like Rheumatoid Arthritis (RA) wherein lymphocytes are recognized as key players. Role of CD8 T cells in RA has been less defined however we found that these cells are activated in RA patients with increased expression of cytolytic granules and inflammatory mediators thereby modulating immune responses contributing to disease severity. Though unconventional expression of different Toll Like Receptors (TLRs) on CD8 T cells has been proposed but their expression and role in T cell activation and differentiation in RA still remains obscure. Herein we report, for the first time, an increased expression of TLR4 on peripheral CD8 T cells of RA patients and its role in skewing CD8 T cells towards activated and inflammatory phenotype thereby playing a significant role in pathogenesis and progression of RA. We found that the surface expression of TLR4 on CD8 T cells directly correlates with disease severity. Moreover, these CD8 T cells respond to the TLR4 ligand LPS and express robust amounts of cytotolytic and inflammatory molecules including TNFα and IFNγ. Our study hence identifies an important role for CD8 T cells in orchestrating RA through TLR4 mediated activation and differentiation.
异常的免疫反应是类风湿关节炎（RA）等自身免疫性疾病的特征，其中淋巴细胞被认为是关键因素。然而，CD8 T 细胞在 RA 中的作用尚未得到明确界定，我们发现这些细胞在 RA 患者中被激活，其细胞毒性颗粒和炎症介质表达增加，从而调节免疫反应，导致疾病严重程度增加。尽管已经提出了 CD8 T 细胞上不同 Toll 样受体（TLR）的非常规表达，但它们在 RA 中 T 细胞激活和分化中的表达和作用仍不清楚。在此，我们首次报道 RA 患者外周血 CD8 T 细胞中 TLR4 的表达增加，及其在将 CD8 T 细胞向激活和炎症表型偏向中的作用，从而在 RA 的发病机制和进展中发挥重要作用。我们发现 CD8 T 细胞表面 TLR4 的表达与疾病严重程度直接相关。此外，这些 CD8 T 细胞对 TLR4 配体 LPS 作出反应，并表达大量细胞毒性和炎症分子，包括 TNFα 和 IFNγ。因此，我们的研究确定了 CD8 T 细胞通过 TLR4 介导的激活和分化在调节 RA 中的重要作用。
