Abstract
Purpose:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Keywords: 432 autoimmune disease •
576 lacrimal gland