| First Author | Zhou J | Year | 2018 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1864 |
| Issue | 7 | Pages | 2438-2447 |
| PubMed ID | 29680668 | Mgi Jnum | J:270460 |
| Mgi Id | MGI:6277741 | Doi | 10.1016/j.bbadis.2018.04.010 |
| Citation | Zhou J, et al. (2018) Anti-IL-7 receptor-alpha treatment ameliorates newly established Sjogren's-like exocrinopathy in non-obese diabetic mice. Biochim Biophys Acta Mol Basis Dis 1864(7):2438-2447 |
| abstractText | The levels of interleukin (IL)-7 and its receptor are elevated in the salivary glands of patients with Sjogren's syndrome (SS). Our previous study indicates that IL-7 plays a critical pathogenic role in the development and onset of SS in a mouse model of this disease. The present study aims at determining whether IL-7 also plays a role in sustaining SS pathologies after the disease onset, by using the non-obese diabetic (NOD) model. Intraperitoneal administration of a blocking antibody against the IL-7 receptor alpha chain (IL-7Ralpha) to female NOD mice aged 10weeks, which exhibited newly onset clinical SS, for the duration of 3weeks significantly ameliorated characteristic SS pathologies including hyposalivation and leukocyte infiltration of the submandibular glands (SMGs). These changes were accompanied by a decrease in IFN-gamma-producing CD4 T- and CD8 T cells, B cells, and lymphocyte chemoattractants CXCL9, -10, -11 and -13 in the SMGs. Anti-IL-7Ralpha treatment markedly diminished the amount of TNF-alpha in the SMGs and increased the level of claudin-1 and aquaporin 5, two molecules critical for normal salivary secretion. Furthermore, neutralization of IFN-gamma and TNF-alpha, individually or in combination, considerably improved salivary secretion, reduced leukocyte infiltration and down-regulated CXCL9 and -13 expression in the SMGs. Collectively, the results indicate that endogenous IL-7R signals promote Th1 and Tc1 responses and IFN-gamma- and TNF-alpha production to sustain the persistence of SS-like sialadenitis in NOD mice. These findings suggest that IL-7 and Th1 cytokines could serve as promising therapeutic targets for this prevalent autoimmune disease. |
