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Yutaka Sakurai, Masataka Ito, Yoko Karasawa, Yoshihiko Usui, Takaaki Hattori, Hiroshi Goto, Masaru Takeuchi; Analysis of chemokines involved in the pathogenesis of dacryoadenitis in mice deficient for programmed cell death-1. Invest. Ophthalmol. Vis. Sci. 2013;54(15):918.
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© ARVO (1962-2015); The Authors (2016-present)
Programmed cell death-1 (PD-1, pdcd1) is one of the costimulatory molecules, negatively regulates the immune responses. Previously, we reported that PD-1-deficient C57BL/6 mice spontaneously develop sjogren syndrome-like dacryoadenitis from 3 months after birth.In this study, we investigated chemokines expression in the lacrimal gland (LG) of pdcd1-/- mice to characterize T cells involved in the development.
The LG were obtained from C57BL/6 pdcd1+/+ and pdcd1-/- mice at 4-,6-,or 12-month-old. The production of CCL1, CCL2, CCL3, CCL4, CCL5, CCL11, CCL12, CCL17, CXCL1, CXCL2, CXCL9, CXCL10, CXCL11, CXCL12, and CXCL13 in the LG of 4-,6-,or 12-month-old pdcd1-/- mice and 4-month-old pdcd1+/+ mice were measured by mouse cytokine array A kit (R&D system). In addition, mRNAs were extracted from the LG, and mRNA expression of CCL3, CCL5, CCL20, CCL22, CXCL9, and CXCL10 in the LG of 4-month-old pdcd1-/- mice and pdcd1+/+ mice were analyzed by real-time PCR.
CCL3, CCL5, CXCL9, and CXCL10 associated with Th1 cell migration were produced in the LG of pdcd1-/- mice compared to pdcd1+/+ mice at 4-month-old. Production of these chemokines related to Th1 cells in the LG of pdcd1-/- mice increased with aging. In the mRNA expression, Pdcd1-/- mice had significantly higher levels of CCL3, CCL5, CXCL9, CXCL10 related to Th1 cells, and CCL20 related to Th17 cells mRNA transcripts in the LG than pdcd1+/+ mice at 4-month-old. Especially, mRNA expression of CCL20 was remarkably higher than others. mRNA expression of CCL22 related to Th2 cells were also detected, but was apparently lower than others.
These results indicate that Th1- and Th17-mediated immune responses are involved in the development of dacryoadenitis in Pdcd1-/- mice, and that Th17 cells play a pivotal role in the pathogenesis.
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