Elevated Expression of Immunoreceptor Tyrosine-Based Inhibitory Motif (TIGIT) on T Lymphocytes is Correlated with Disease Activity in Rheumatoid Arthritis

Abstract

BackgroundIt is well known that lymphocytes play an important role in rheumatoid arthritis (RA). T cell immunoreceptors with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (TIGIT) have immunosuppressive co-stimulatory molecules that mediate inhibitory effects, but their roles in RA are poorly understood.Material/MethodsWere recruited 76 patients with RA and 33 healthy controls (HC). Clinical manifestations, laboratory measurements, physical examination, and medical history of RA patients were recorded. The expression of TIGIT on CD3+ T lymphocytes, B lymphocytes, monocytes, neutrophils, CD3+CD4+ T lymphocytes, and CD3+CD8+ T lymphocytes was determined using flow cytometry. The expression of TIGIT on T lymphocytes in patients with RA was further analyzed to investigate its correlations with markers of autoimmune response, inflammation, and disease activity in RA.ResultsCompared with HC, the expression levels of TIGIT on CD3+CD4+ T lymphocytes and CD3+CD8+ T lymphocytes were significantly increased in patients with RA (P < 0.01). The frequency of TIGIT-expressing CD3+CD4+ T lymphocytes was positively correlated with RF, increased ACPA, ESR, and CRP levels. The frequency of TIGIT-expressing CD3+CD8+ T lymphocytes was positively correlated with RF and ESR levels. Furthermore, the expression level of TIGIT on CD3+CD4+ T lymphocytes was positively correlated with the DAS28 score in RA.ConclusionsThe expression levels of TIGIT on T lymphocytes were elevated and correlated with disease activity in RA.

RNA-seq reveals the circular RNA and miRNA expression profile of peripheral blood mononuclear cells in patients with rheumatoid arthritis

“…RA is a systemic autoimmune disease with unknown etiology. In previous decades, great efforts have been made to explore the molecular mechanisms of RA [13,14]; however, the majority of previous studies have concentrated on protein-coding genes. Rapidly accumulating evidence has now suggested that although noncoding RNAs do not directly encode proteins, they play a regulatory role in the transcription and translation of protein-coding genes [15].…”

Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and Target to Regulate Effector Cellular Responses in Rheumatoid Arthritis

“…Increased expression of TIGIT on the surface of CD4+ T cells was recently shown to be associated with a higher DAS28 and increased evidence of inflammation in RA patients (27). Given that T cell activation results in the transient up-regulation of some inhibitory receptors (18), it is likely that the TIGIT+ T cells identified by Luo and colleagues (27) include activated T cells with increased potential to proliferate and produce effector cytokines.…”

“…Increased expression of TIGIT on the surface of CD4+ T cells was recently shown to be associated with a higher DAS28 and increased evidence of inflammation in RA patients (27). Given that T cell activation results in the transient up-regulation of some inhibitory receptors (18), it is likely that the TIGIT+ T cells identified by Luo and colleagues (27) include activated T cells with increased potential to proliferate and produce effector cytokines. In contrast, our results indicated that the inhibitory receptor-expressing CD8+ T cells from RA patients with low levels of T cell activation are more likely undergoing terminal differentiation (i.e., exhaustion), a T cell differentiation stage associated with sustained expression of multiple inhibitory receptors (28).…”

Expression of T‐cell immunoglobulin and immunoreceptor tyrosine‐based inhibitory motif domain on CD4+ T cells in patients with atopic dermatitis

“…Consistent with this, TIGIT expression on CD4 + T cells is elevated in patients with rheumatoid arthritis and systemic lupus erythematosus. [17][18][19] However, TIGIT expression on CD4 + T cells was augmented in patients with mild AD but reduced in those with severe AD, suggesting that TIGIT expression may be impaired in a subset of patients with AD, leading to the deterioration of skin inflammation.…”