The role of B7 family costimulatory molecules and indoleamine 2,3-dioxygenase in primary Sjögren’s syndrome and systemic sclerosis

Abstract

B7 costimulatory molecules are present on antigenpresenting cells (APCs) and influence intracellular expression of indoleamine 2,3-dioxygenase (IDO), a molecule with important immunoregulatory functions. We determined the frequency of activated (CD11b+) monocytes expressing B7-1, B7-2, B7-H1, and B7-H2 molecules, and that of CD3+ and CD4+ T cells expressing the corresponding CD28, CTLA-4, PD-1, and ICOS receptors in peripheral blood samples of 20 healthy adults and 9 SSc and 15 pSS patients using flow cytometry. We also examined the intracellular expression of IDO. The expression of CD28 was lower in both SSc and pSS patients. The frequency of CTLA-4 was increased in pSS. The expression of ICOS, a stimulator of T cell activation, was elevated in pSS, but not in SSc, while that of its corresponding costimulatory molecule, B7-H2, was strongly decreased in SSc compared to controls. The frequency of PD-1 expressing T lymphocytes was decreased in both pSS and SSc. The frequency of IDO-expressing APCs, as well as intracellular IDO content in T cells was higher in pSS than in controls. Our investigation identified a number of differences in B7 costimulation between SSc and pSS patients which may play a role in the distinct pathogenesis and clinical features of these autoimmune disorders.

Molecular profile and proangiogenic activity of the adipose-derived stromal vascular fraction used as an autologous innovative medicinal product in patients with systemic sclerosis

“…In addition to its well-known immunoregulatory functions, IDO1 was shown to be involved in the regulation of endothelial function, vascular tone, angiogenesis and atherogenesis processes 43. Consistent with our results, IDO is emerging as a key regulator of innate and adaptive immune inflammatory responses in SSc 44. Thus, upregulation of IDO in SVF could be a compensatory mechanism that counteracts endothelial inflammation, dysangiogenesis and immune activation.…”

Neurological and Inflammatory Manifestations in Sjögren’s Syndrome: The Role of the Kynurenine Metabolic Pathway

“…Measurements of IDO in antigen-presenting cells (APCs) and in T cells have demonstrated higher levels in the peripheral blood cells of pSS patients than controls matched by age and sex, also while using specific antibodies and flow cytometry, despite the heterogeneity of the groups and the high internal variability of the results [217]. Therefore, the T cell-mediated autoimmune activity present in autoimmune diseases, including SLE and SS, has been associated with elevated activity of the KP; however, the effects on autoantigen stimulation and IFN-γ activity remain unknown [216,217].…”

“…Considering the broad spectrum of substrates, target tissues, and alternative effects of KP, therapeutic strategies to interfere with different steps have resulted in one or more of the following outcomes: attenuation of inflammation, reduction of chronic pain or improvement of fatigue, and depressive feelings in SS [18,217,233].…”

Kynurenines in the Pathogenesis of Multiple Sclerosis: Therapeutic Perspectives

“…Analysis of the peripheral blood with flow cytometry of Sjögren's syndrome patients detected higher expression of IDO-1 in the patients' dendritic cells as compared to the dendritic cells of healthy controls [161]. Additionally, overexpression of IDO was demonstrated in both T cells and antigen-presenting cells (APC) of Sjögren's syndrome patients, compared to healthy controls [161,162].…”