TY - JOUR
T1 - Spontaneous autoimmune dacryoadenitis in aged CD25KO mice
AU - Rahimy, Ehsan
AU - Pitcher, John D.
AU - Pangelinan, Solherny B.
AU - Chen, Wei
AU - Farley, William J.
AU - Niederkorn, Jerry Y.
AU - Stern, Michael E.
AU - Li, De Quan
AU - Pflugfelder, Stephen C.
AU - De Paiva, Cintia S.
N1 - Funding Information:
Supported by National Institutes of Health grants EY11915 (S.C.P.); Fight for Sight grants-in-aid (C.S.D.P.); Hartford Foundation (C.S.D.P.); Research to Prevent Blindness, Oshman Foundation; William Stamps Farish Fund; Hamill Foundation and an unrestricted grant from Allergan Inc. The sponsor agencies had no involvement on the study design; data collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
PY - 2010/8
Y1 - 2010/8
N2 - To investigate time-related immunopathological changes in the lacrimal glands (LGs) of CD25KO mice, we examined LGs of C57BL/6 (wild-type) and CD25KO mice at 8, 12, and 16 weeks of age. T cell infiltration was quantified by flow cytometry, and gland function by tear peroxidase activity and epidermal growth factor mRNA expression. T helper (Th)-1, -2 and -17-associated cytokine expression was evaluated by real-time PCR. Epithelial apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and activated caspase-3 staining. Eight-week-old CD25KO mice demonstrated significantly increased numbers of CD4 and CD8 T cells infiltrating the LGs. This peaked at 12 weeks of age. No peroxidase secretion was detected, and epidermal growth factor mRNA expression was barely detected in CD25KO mice. Ductal epithelial apoptosis was noted in CD25KO mice. Young CD25KO LGs had higher Th-17- (interleukin [IL]-23R, transforming growth factor-β1, IL-17A, CC chemokine attractant ligand-20) and Th-1-associated cytokine transcripts (interferon-γ, T-bet, IL-12, IL-2, IL-18) than young wild-type LGs. There was also a significant time-related decrease in IL-17A and CC chemokine attractant ligand-20 in CD25KO LGs. Taken together, autoimmune LG infiltration with loss of LG function was observed in CD25KO mice as early as 8 weeks of age. Time-related switch from Th-17 to Th-1 inflammation was noted in CD25KO mice.
AB - To investigate time-related immunopathological changes in the lacrimal glands (LGs) of CD25KO mice, we examined LGs of C57BL/6 (wild-type) and CD25KO mice at 8, 12, and 16 weeks of age. T cell infiltration was quantified by flow cytometry, and gland function by tear peroxidase activity and epidermal growth factor mRNA expression. T helper (Th)-1, -2 and -17-associated cytokine expression was evaluated by real-time PCR. Epithelial apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and activated caspase-3 staining. Eight-week-old CD25KO mice demonstrated significantly increased numbers of CD4 and CD8 T cells infiltrating the LGs. This peaked at 12 weeks of age. No peroxidase secretion was detected, and epidermal growth factor mRNA expression was barely detected in CD25KO mice. Ductal epithelial apoptosis was noted in CD25KO mice. Young CD25KO LGs had higher Th-17- (interleukin [IL]-23R, transforming growth factor-β1, IL-17A, CC chemokine attractant ligand-20) and Th-1-associated cytokine transcripts (interferon-γ, T-bet, IL-12, IL-2, IL-18) than young wild-type LGs. There was also a significant time-related decrease in IL-17A and CC chemokine attractant ligand-20 in CD25KO LGs. Taken together, autoimmune LG infiltration with loss of LG function was observed in CD25KO mice as early as 8 weeks of age. Time-related switch from Th-17 to Th-1 inflammation was noted in CD25KO mice.
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U2 - 10.2353/ajpath.2010.091116
DO - 10.2353/ajpath.2010.091116
M3 - Article
C2 - 20566743
AN - SCOPUS:77957259265
SN - 0002-9440
VL - 177
SP - 744
EP - 753
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 2
ER -