Background Indoleamine 2,3 dioxygenase 1 and 2 (IDO1-IDO2) enzymes catabolise tryptophan (TR) to its metabolite kyurenine (KNR), and are competitively inhibited by 1-Methyl-TR (1M-TR). IDO1-IDO2, once activated in dendritic cells (DCs) by IFN-type 1, may induce immune-tolerance by suppressing antigen-specific T-cell response directly or by activating T-reg cells . The role of IDO in autoimmune diseases has not been completely elucidated. In collagen-induced arthritis of DBA/1 mice, IDO1 limits the arthritis phenotype, as shown by the detrimental effect of 1M-TR treatment. Conversely, in auto-reactive B-cell-mediated arthritis of K/BxN transgenic mice, IDO1 sustains the autoimmune aggression, as demonstrated by arthritis improvement and auto-reactive B-cell reduction in draining lymph nodes after 1M-TR treatment . Finally, significantly increased plasma KNR levels and KNR/TR ratio have been reported in patients with systemic lupus and Sjogren's syndrome (SS) .
Objectives To verify whether IDO1 is activated in SS focal sialoadenitis (FS), and investigate the relationships between IDO1 expression and the main cellular components in inflammatory foci.
Methods Minor salivary gland biopsies from 22 patients (1 male, 21 females) with SS were examined for IDO1 expression using anti-IDO1 antibodies (Abs), and immuno-histochemistry (IHC). Prevalence of B-cells, T-cells, and plasmacytoid (p) DCs was investigated in FS infiltrates using monoclonal anti-CD20, -CD3, and -CD123 Abs, respectively. Immuno-fluorescence (IF) was used to evaluate the co-localization of IDO1+ cells with the immune cells within SS FS.
Results Patients were aged 15-77 yrs. (mean 53.4 yrs), and their disease duration ranged from 1 to 16 yrs. (mean 8.9 yrs.). Anti-Ro/La Abs and extra-glandular features were recorded in 15 and 14 patients, respectively. IHC analysis demonstrated consistent expression of IDO1 within the focal infiltrates. A semi-quantitative IHC score showed significant correlation between IDO1 expression and FS scores (Spearman R=0.52, p<.02), prevalence of CD20+B-cells (R=0.79, p<.0005), and number of CD123+pDCs (R=0.64, p<.005), but not with the CD3+T-cells (R=0.14, p=ns). IF analysis of FS infiltrates characterized by germinal centre-like organization demonstrated presence of IDO1+ cells around the B-cell area and at the boundaries of the T cell rich zone.
Conclusions IDO1 activity is present in SS FS, and appears to be related to the amount of pDCs and B-cells. Further investigations are needed to clarify the cell type(s) expressing IDO1 within the SS FS infiltrates and the immuno-regulatory role of this enzyme in SS.
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Disclosure of Interest None declared
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