Age-related T-cell cytokine profile parallels corneal disease severity in Sjögren's syndrome-like keratoconjunctivitis sicca in CD25KO mice

Cintia S. de Paiva, Cindy S. Hwang, John D. Pitcher, Solherny B. Pangelinan, Ehsan Rahimy, Wei Chen, Kyung Chul Yoon, William J. Farley, Jerry Y. Niederkorn, Michael E. Stern, De Quan Li, Stephen C. Pflugfelder

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Objectives. IL-2rα (CD25)-/- mice develop autoimmunity and lymphoproliferative disorders, including SS-like disease. The objective of this study was to evaluate the severity of corneal epithelial disease and T-cell cytokine profile in the ocular surface tissues of CD25KO mice. Methods. CD25KO mice were evaluated at 8, 12 and 16 weeks of age. Corneal epithelial smoothness and corneal permeability were measured. Phenotype of infiltrating lymphocytes was evaluated by immunohistochemistry. Th-1, -2 and -17 associated factors were measured by real-time PCR in cornea and conjunctiva and by Luminex immunobead assay in tears. Results. Compared with 8-week-old wild-type (WT) mice, CD25KO mice of the same age had significantly greater corneal irregularity and a significant increase in the number of CD4+ and CD8+ T cells infiltrating the conjunctiva. CD25KO mice had significantly higher levels of IL-6, TGF-β1, IL-23R, IL-17A, IL-17F, IL-21, CCL20, IL-10, GATA-3 and IFN-γ mRNA transcripts in their cornea and conjunctiva than WT mice at 8 weeks. IL-17A and IL-17F mRNA transcripts peaked at 12 weeks, whereas IFN-γ spiked at 16 weeks in CD25KO mice. Increased expression of IL-17A and IL-17F at 12 weeks in CD25KO mice was accompanied by a worsening of corneal surface parameters and an increase of CD4+ T cell infiltrating the cornea. Conclusions. Disruption of IL-2 signalling in CD25KO mice results in age-dependent SS-like autoimmune lacrimal-keratoconjunctivitis. A mix of Th-1 and Th-17 cytokines was detected. The peak severity of corneal epithelial disease corresponded to the peak of IL-17 expression.

Original languageEnglish (US)
Article numberkep357
Pages (from-to)246-258
Number of pages13
JournalRheumatology
Volume49
Issue number2
DOIs
StatePublished - Feb 2010

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Keratoconjunctivitis Sicca
Corneal Diseases
Interleukin-17
Cytokines
T-Lymphocytes
Conjunctiva
Cornea
Tears
Keratoconjunctivitis
Messenger RNA
Lymphoproliferative Disorders
Autoimmunity
Interleukin-1
Interleukin-10
Interleukin-2
Real-Time Polymerase Chain Reaction
Permeability
Interleukin-6
Immunohistochemistry

Keywords

  • CD4 T cell
  • Cytokines
  • Dry eye
  • IFN-γ
  • IL-17
  • Sjögren's syndrome
  • Th-17

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

Cite this

de Paiva, C. S., Hwang, C. S., Pitcher, J. D., Pangelinan, S. B., Rahimy, E., Chen, W., ... Pflugfelder, S. C. (2010). Age-related T-cell cytokine profile parallels corneal disease severity in Sjögren's syndrome-like keratoconjunctivitis sicca in CD25KO mice. Rheumatology, 49(2), 246-258. [kep357]. https://doi.org/10.1093/rheumatology/kep357

Age-related T-cell cytokine profile parallels corneal disease severity in Sjögren's syndrome-like keratoconjunctivitis sicca in CD25KO mice. / de Paiva, Cintia S.; Hwang, Cindy S.; Pitcher, John D.; Pangelinan, Solherny B.; Rahimy, Ehsan; Chen, Wei; Yoon, Kyung Chul; Farley, William J.; Niederkorn, Jerry Y.; Stern, Michael E.; Li, De Quan; Pflugfelder, Stephen C.

In: Rheumatology, Vol. 49, No. 2, kep357, 02.2010, p. 246-258.

Research output: Contribution to journalArticle

de Paiva, CS, Hwang, CS, Pitcher, JD, Pangelinan, SB, Rahimy, E, Chen, W, Yoon, KC, Farley, WJ, Niederkorn, JY, Stern, ME, Li, DQ & Pflugfelder, SC 2010, 'Age-related T-cell cytokine profile parallels corneal disease severity in Sjögren's syndrome-like keratoconjunctivitis sicca in CD25KO mice', Rheumatology, vol. 49, no. 2, kep357, pp. 246-258. https://doi.org/10.1093/rheumatology/kep357
de Paiva, Cintia S. ; Hwang, Cindy S. ; Pitcher, John D. ; Pangelinan, Solherny B. ; Rahimy, Ehsan ; Chen, Wei ; Yoon, Kyung Chul ; Farley, William J. ; Niederkorn, Jerry Y. ; Stern, Michael E. ; Li, De Quan ; Pflugfelder, Stephen C. / Age-related T-cell cytokine profile parallels corneal disease severity in Sjögren's syndrome-like keratoconjunctivitis sicca in CD25KO mice. In: Rheumatology. 2010 ; Vol. 49, No. 2. pp. 246-258.
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abstract = "Objectives. IL-2rα (CD25)-/- mice develop autoimmunity and lymphoproliferative disorders, including SS-like disease. The objective of this study was to evaluate the severity of corneal epithelial disease and T-cell cytokine profile in the ocular surface tissues of CD25KO mice. Methods. CD25KO mice were evaluated at 8, 12 and 16 weeks of age. Corneal epithelial smoothness and corneal permeability were measured. Phenotype of infiltrating lymphocytes was evaluated by immunohistochemistry. Th-1, -2 and -17 associated factors were measured by real-time PCR in cornea and conjunctiva and by Luminex immunobead assay in tears. Results. Compared with 8-week-old wild-type (WT) mice, CD25KO mice of the same age had significantly greater corneal irregularity and a significant increase in the number of CD4+ and CD8+ T cells infiltrating the conjunctiva. CD25KO mice had significantly higher levels of IL-6, TGF-β1, IL-23R, IL-17A, IL-17F, IL-21, CCL20, IL-10, GATA-3 and IFN-γ mRNA transcripts in their cornea and conjunctiva than WT mice at 8 weeks. IL-17A and IL-17F mRNA transcripts peaked at 12 weeks, whereas IFN-γ spiked at 16 weeks in CD25KO mice. Increased expression of IL-17A and IL-17F at 12 weeks in CD25KO mice was accompanied by a worsening of corneal surface parameters and an increase of CD4+ T cell infiltrating the cornea. Conclusions. Disruption of IL-2 signalling in CD25KO mice results in age-dependent SS-like autoimmune lacrimal-keratoconjunctivitis. A mix of Th-1 and Th-17 cytokines was detected. The peak severity of corneal epithelial disease corresponded to the peak of IL-17 expression.",
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T1 - Age-related T-cell cytokine profile parallels corneal disease severity in Sjögren's syndrome-like keratoconjunctivitis sicca in CD25KO mice

AU - de Paiva, Cintia S.

AU - Hwang, Cindy S.

AU - Pitcher, John D.

AU - Pangelinan, Solherny B.

AU - Rahimy, Ehsan

AU - Chen, Wei

AU - Yoon, Kyung Chul

AU - Farley, William J.

AU - Niederkorn, Jerry Y.

AU - Stern, Michael E.

AU - Li, De Quan

AU - Pflugfelder, Stephen C.

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N2 - Objectives. IL-2rα (CD25)-/- mice develop autoimmunity and lymphoproliferative disorders, including SS-like disease. The objective of this study was to evaluate the severity of corneal epithelial disease and T-cell cytokine profile in the ocular surface tissues of CD25KO mice. Methods. CD25KO mice were evaluated at 8, 12 and 16 weeks of age. Corneal epithelial smoothness and corneal permeability were measured. Phenotype of infiltrating lymphocytes was evaluated by immunohistochemistry. Th-1, -2 and -17 associated factors were measured by real-time PCR in cornea and conjunctiva and by Luminex immunobead assay in tears. Results. Compared with 8-week-old wild-type (WT) mice, CD25KO mice of the same age had significantly greater corneal irregularity and a significant increase in the number of CD4+ and CD8+ T cells infiltrating the conjunctiva. CD25KO mice had significantly higher levels of IL-6, TGF-β1, IL-23R, IL-17A, IL-17F, IL-21, CCL20, IL-10, GATA-3 and IFN-γ mRNA transcripts in their cornea and conjunctiva than WT mice at 8 weeks. IL-17A and IL-17F mRNA transcripts peaked at 12 weeks, whereas IFN-γ spiked at 16 weeks in CD25KO mice. Increased expression of IL-17A and IL-17F at 12 weeks in CD25KO mice was accompanied by a worsening of corneal surface parameters and an increase of CD4+ T cell infiltrating the cornea. Conclusions. Disruption of IL-2 signalling in CD25KO mice results in age-dependent SS-like autoimmune lacrimal-keratoconjunctivitis. A mix of Th-1 and Th-17 cytokines was detected. The peak severity of corneal epithelial disease corresponded to the peak of IL-17 expression.

AB - Objectives. IL-2rα (CD25)-/- mice develop autoimmunity and lymphoproliferative disorders, including SS-like disease. The objective of this study was to evaluate the severity of corneal epithelial disease and T-cell cytokine profile in the ocular surface tissues of CD25KO mice. Methods. CD25KO mice were evaluated at 8, 12 and 16 weeks of age. Corneal epithelial smoothness and corneal permeability were measured. Phenotype of infiltrating lymphocytes was evaluated by immunohistochemistry. Th-1, -2 and -17 associated factors were measured by real-time PCR in cornea and conjunctiva and by Luminex immunobead assay in tears. Results. Compared with 8-week-old wild-type (WT) mice, CD25KO mice of the same age had significantly greater corneal irregularity and a significant increase in the number of CD4+ and CD8+ T cells infiltrating the conjunctiva. CD25KO mice had significantly higher levels of IL-6, TGF-β1, IL-23R, IL-17A, IL-17F, IL-21, CCL20, IL-10, GATA-3 and IFN-γ mRNA transcripts in their cornea and conjunctiva than WT mice at 8 weeks. IL-17A and IL-17F mRNA transcripts peaked at 12 weeks, whereas IFN-γ spiked at 16 weeks in CD25KO mice. Increased expression of IL-17A and IL-17F at 12 weeks in CD25KO mice was accompanied by a worsening of corneal surface parameters and an increase of CD4+ T cell infiltrating the cornea. Conclusions. Disruption of IL-2 signalling in CD25KO mice results in age-dependent SS-like autoimmune lacrimal-keratoconjunctivitis. A mix of Th-1 and Th-17 cytokines was detected. The peak severity of corneal epithelial disease corresponded to the peak of IL-17 expression.

KW - CD4 T cell

KW - Cytokines

KW - Dry eye

KW - IFN-γ

KW - IL-17

KW - Sjögren's syndrome

KW - Th-17

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