Salivary gland tissue expression of interleukin-23 and interleukin-17 in Sjögren's syndrome: findings in humans and mice.
OBJECTIVE
Recently, the Th1/Th2 paradigm has been expanded by the discovery of Th17 cells, a subset of CD4+ memory T cells characterized by their unique ability to secrete interleukin-17 (IL-17) family cytokines. Importantly, Th17 cells appear to be intimately involved in autoimmunity. We undertook the present study to investigate whether the Th17/IL-23 system is up-regulated in Sjögren's syndrome (SS).


METHODS
Sera, saliva, and salivary glands from C57BL/6.NOD-Aec1Aec2 mice (a model for primary SS), as well as sera, saliva, and salivary gland biopsy specimens obtained from patients with primary SS, were evaluated for IL-17 and IL-23 expression by immunohistochemistry, real-time polymerase chain reaction, and the Luminex system.


RESULTS
Immunohistochemical stainings of submandibular glands from C57BL/6.NOD-Aec1Aec2 mice and of salivary gland biopsy specimens from SS patients revealed strong positive staining for both IL-17 and IL-23 within lymphocytic foci and diffuse staining on epithelial tissues. Temporal expression of IL-17 and IL-23 in submandibular glands of C57BL/6.NOD-Aec1Aec2 mice correlated with expression of retinoic acid-related orphan receptor gammat, the Th17 cell master control gene. While IL-17 could not be detected in saliva from 4-20-week-old C57BL/6.NOD-Aec1Aec2 mice, this cytokine was present in the blood of mice up to age 16 weeks. This contrasted with sera and saliva from SS patients, in which IL-17 and IL-6 were present at varying levels.


CONCLUSIONS
These results suggest that the Th17/IL-23 system is up-regulated in C57BL/6.NOD-Aec1Aec2 mice and SS patients at the time of disease. A correlation between up-regulated IL-17/IL-23 expression and specific clinical manifestations of SS has yet to be identified.
Nguyen
Cuong Q
CQ
Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32610, USA. Nguyen@pathology.ufl.edu
Hu
Min H
MH
Li
Yi
Y
Stewart
Carol
C
Peck
Ammon B
AB
D000818:Animals; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D012463:Saliva / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000378:metabolism* / Q000473:pathology
D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6