Abstract
The etiology of Behçet’s disease (BD), a chronic, multisystemic autoinflammatory and autoimmune disease, remains unknown; however, researchers have postulated that infectious agents, such as herpes simplex virus, are significant triggering factors of BD. Tripartite motif-containing (TRIM) proteins exhibit antiviral properties, mediating antiviral defense mechanisms. The purpose of this study was to investigate TRIM21 protein expression in the monocytes of BD patients and to identify the role of TRIM21 in immune dysregulation in BD. In this study, the expression of TRIM21 and related molecules, including interferon regulatory factor 8 (IRF8), was analyzed in monocytes from BD patients. Functional analyses using small interfering RNA and co-culture with responder T cells were performed to examine the pathological role of TRIM21 in BD. Peripheral blood monocytes from BD patients showed increased TRIM21 expression and decreased IRF8 expression compared with that in monocytes from healthy controls. TRIM21 was found to decrease IRF8 expression. BD monocytes facilitated Th1 and Th17 differentiation of co-cultured T cells, and knock-down of TRIM21 expression by small interfering RNA inhibited this differentiation. In conclusion, TRIM21 played a pivotal role in regulating the secretion of proinflammatory cytokines in monocytes of BD patients.
Highlights
The tripartite motif-containing (TRIM) family of proteins has been recognized for its role in regulating the innate immune response to viral infections
To confirm the clinical significance of TRIM21 in Behçet’s disease (BD), we first examined the expression of TRIM21 in freshly isolated monocytes from BD patients and healthy controls
Western blot analysis showed that TRIM21 expression in monocytes was significantly higher in BD patients (n = 18) than in healthy controls (n = 5) (P = 0.0009, Fig. 1a and b)
Summary
The tripartite motif-containing (TRIM) family of proteins has been recognized for its role in regulating the innate immune response to viral infections. TRIM21 is an E3 ubiquitin ligase that regulates innate immune responses by ubiquitinating various intracellular proteins, such as nuclear factor kappa B (NF-kB) and interferon (IFN) regulatory factors (IRFs). Multiple IRFs are tightly regulated by TRIM21 in immune cells[2]. Because human monocytes trigger and polarize Th responses and regulate T-cell responses during infection and in autoimmune diseases, monocytes and their progeny, such as macrophages, appear to play an important role in BD pathogenesis[11,12,13]. We sought to elucidate TRIM21 protein expression in monocytes of BD patient and to identify the role of TRIM21 on Th1/Th17 immune deviation in BD
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