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Abstract Background Idiopathic orbital inflammation (IOI) is a nonspecific orbital inflammatory disease with the third highest prevalence among orbital diseases, and its pathogenesis is associated with T-cell-mediated immune responses. This study aimed to investigate the differences in T-cell receptor (TCR) expression between IOI patients and healthy subjects by high-throughput sequencing and to characterize TCR expression in patients with IOI and with respect to glucocorticoid response. Methods A total of 19 subjects were enrolled in this study and were divided into the idiopathic orbital inflammation group (IOI group, n = 13) and the healthy control group (HC group, n = 6), and within the IOI group were further divided into the glucocorticoid therapy sensitive group (IOI(EF) group, n = 6) and the glucocorticoid therapy ineffective group (IOI(IN) group, n = 7) based on the degree of effectiveness to glucocorticoid therapy. High-throughput TCR sequencing was performed on peripheral blood mononuclear cells of IOI patients and healthy control individuals using 5’ RACE technology combined with Unique Identifier (UID) digital tag correction technology. The TCR CDR3 region diversity, sharing patterns, and differential sequences between the IOI and HC groups, and between the IOI(EF) and IOI(IN) groups were analyzed. Results It was found that the diversity of TCR CDR3 in the IOI group was significantly lower than that in the HC group, and the frequency of V gene use was significantly different between groups. The diversity of TCR CDR3 in patients in the IOI(EF) group was significantly lower than that in patients in the IOI(IN) group, and the frequency of V and J gene use was significantly different between the IOI(EF) group and the IOI(IN) group. Additionally, we found 133 nucleotide sequences shared in all IOI samples and screened two sequences with higher expression from them. Conclusions Our results suggested that abnormal clonal expansion of specific T-cells exists in IOI patients and that TCR diversity may had an impact on the prognosis of glucocorticoid-treated IOI. This study may contribute to a better understanding of the immune status of IOI and provide new insights for T-cell -associated IOI pathogenesis, diagnosis and treatment prediction.

Abstract Orbital inflammatory pseudotumor (OIP) is a benign, non-specific inflammatory disorder that commonly occurs in middle-aged adults and is usually unilateral but can occur bilaterally. Its clinical manifestations have tremendous clinical heterogeneity and vary according to the site of infiltration and the degree of lesions, including orbital pain, swelling, diplopia, proptosis, restricted eye movement, and decreased visual acuity. Clinical features, Image characteristics and pathological examinations often need to be evaluated to confirm the diagnosis. Currently, there is no systematic research on the pathogenesis of OIP, which may be related to immunity or infection. The first-line treatment is glucocorticoids. Radiotherapy, immunosuppressants, and biologics can be considered for treatment-resistant, hormone-dependent, or intolerant patients. In this review, we aim to summarize and focus on new insights into OIP, including new diagnostic criteria, pathogenesis, and discoveries in new drugs and treatment strategies. In particular, we highlight the literature and find that T cell-mediated immune responses are closely related to the pathogenesis of OIP. Further exploration of the mechanism and signaling pathway of T cells in the immune process will help to identify their therapeutic targets and carry out targeted therapy to treat refractory OIP and reduce the side effects of traditional treatments.

Abstract Background The glutamine synthetase (GS), an astrocyte-specific enzyme, is involved in lipopolysaccharide (LPS)-induced inflammation which activates the mitogen-activated protein kinase (MAPK) signaling. Endocannabinoid 2-arachidonyl glycerol (2-AG) has been described to serve as an endogenous mediator of analgesia and neuroprotection. However, whether 2-AG can directly influence astrocytic GS and MAPK expressions remains unknown. Methods In the present study, the effects of 2-AG on astrocytic GS expression, p38 and ERK1/2 expression, cell viability, and apoptosis following LPS exposure were investigated. Results The results revealed that LPS exposure increased GS expression with p38 activation in the early phase and decreased GS expression with activation of ERK1/2, decrease of cell viability, and increase of apoptosis in the late phase. Inhibition of p38 reversed GS increase in the early phase while inhibition of ERK1/2 reversed GS decrease in the late phase induced by LPS exposure. 2-AG protected astrocytes from increase of apoptosis and decrease of cell viability induced by the late phase of LPS exposure. In the early phase of LPS exposure, 2-AG could suppress the increase of GS expression and activation of p38 signaling. In the late phase of LPS exposure, 2-AG could reverse the decrease of GS expression and activation of ERK1/2 induced by LPS. Conclusion These findings suggest that 2-AG could maintain the GS expression in astrocytes to a relatively stable level through modulating MAPK signaling and protect astrocytes from LPS exposure.