Local suppression of IL-21 in submandibular glands retards the development of Sjögren's syndrome in non-obese diabetic mice.
BACKGROUND
The aim of this study was to verify the validity of IL-21 local suppression in submandibular glands of preventing the development of Sjögren's syndrome in non-obese diabetic (NOD) mice and figure out the mechanism.


METHODS
IL-21 levels in submandibular glands were suppressed by ductal cannulation of IL-21 shRNA lentivirus. Then, saliva flow rates (SFR) and histopathologic changes of submandibular glands were measured to assess the severity of disease development. Real-time PCR, flow cytometry, and immunohistochemistry were used to detect the changes of T helper cells and related cytokines.


RESULTS
The reduction in SFRs in NOD mice was significantly alleviated from 9 to 17 weeks of age along with the suppression of IL-21 in submandibular glands. Lymphocytic infiltration was also milder than control NOD mice. Moreover, the lower level of IL-21 led to the down-regulation of follicular helper T (Tfh) cells.


CONCLUSIONS
Local suppression of IL-21 in submandibular glands could retard the development of Sjögren's syndrome in NOD mice. IL-21 might contribute to the development of B-cell disorder in Sjögren's syndrome via Tfh cells pathway.
Shandong Provincial Key Laboratory of Oral Biomedicine, School of Stomatology, Shandong University, Jinan, China.
Hao
H
Liu
Guoxin
G
Liu
Lei
L
Gong
Yan
Y
Zhang
Guangshui
G
Jiang
D000818:Animals; D018791:CD4 Lymphocyte Count; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D012313:RNA / Q000032:analysis; D034741:RNA, Small Interfering / Q000627:therapeutic use; D011897:Random Allocation; D012472:Salivation / Q000502:physiology*; D012859:Sjogren's Syndrome / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013363:Submandibular Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000098546:Interleukin-21
D016207:Cytokines; D007378:Interleukins; D034741:RNA, Small Interfering; D012313:RNA; D000098546:Interleukin-21