Disease Biology Laboratory, School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), Deemed to be University, Bhubaneswar, Odisha, India.
Department of Rheumatology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India.
Immunobiology. 2023 Jul;228(4):152415. doi: 10.1016/j.imbio.2023.152415. Epub 2023 Jun 20.
The T cells, components of adaptive immunity participate in immune pathology of the autoimmune inflammatory disorder called rheumatoid arthritis (RA). The presence of TLRs on the surface of the CD8 T cells and their ability to recognize bacterial moieties adds to the inflammatory burden in case of RA. It has been reported that the gut microbiome is necessary for the crucial shift in the balance between proinflammatory and anti-inflammatory cytokines. The altered gut microbiome and the presence of TLRs emphasizes on the microbiome driven inflammatory responses in case of RA.
Eighty-nine RA patients participated in this study. Clinical variations like disease duration, number of actively inflamed joints, number and type of bone deformities, CRP, RF, Anti-CCP, ESR, DAS 28 score were recorded for each patient. Co-culture of CD8T cells and bacteria has been performed with proper culture condition. TLRs and inflammatory mediators' expression level were checked by both qPCR and flow cytometry analysis.
We observed in the suppression of pro-inflammatory molecules like Granzyme B and IFNƳ and expression of TLR2 in CD8 + T cells upon treatment with Lactobacillus rhamnosus (L. rhamnosus). Moreover, L. rhamnosus activated CD8T cells such that they could induce FOXP3 expression in CD4T cells thereby skewing T cell population towards a regulatory phenotype. On the contrary, TLR4 engagement on CD8T cell by Escherichia coli (E.coli) increased in inflammatory responses following ERK activation.
Thus, we conclude that L. rhamnosus can effectively suppress CD8T cell mediated inflammation by a simultaneous decrease of Th1 cells that may potentiate better treatment modalities for RA.
适应性免疫的 T 细胞参与了一种名为类风湿关节炎（RA）的自身免疫性炎症疾病的免疫病理过程。CD8 T 细胞表面存在 TLRs，并且能够识别细菌成分，这增加了 RA 中的炎症负担。据报道，肠道微生物组对于促炎细胞因子和抗炎细胞因子之间平衡的关键转变是必要的。改变的肠道微生物组和 TLRs 的存在强调了 RA 中微生物组驱动的炎症反应。
89 名 RA 患者参与了这项研究。记录了每位患者的临床变化，如疾病持续时间、活跃炎症关节的数量、骨畸形的数量和类型、CRP、RF、抗 CCP、ESR、DAS28 评分。在适当的培养条件下进行了 CD8T 细胞和细菌的共培养。通过 qPCR 和流式细胞术分析检查 TLRs 和炎症介质的表达水平。
我们观察到，在用罗伊氏乳杆菌（L. rhamnosus）处理后，CD8+T 细胞中促炎分子（如 Granzyme B 和 IFNγ）的表达受到抑制，TLR2 的表达也受到抑制。此外，L. rhamnosus 激活了 CD8T 细胞，使其能够在 CD4T 细胞中诱导 FOXP3 表达，从而使 T 细胞群体向调节表型倾斜。相反，大肠杆菌（E.coli）通过 TLR4 与 CD8T 细胞的相互作用，在 ERK 激活后增加了炎症反应。
因此，我们得出结论，L. rhamnosus 可以通过同时减少 Th1 细胞来有效抑制 CD8T 细胞介导的炎症，这可能为 RA 提供更好的治疗方法。
