| First Author | De Paiva CS | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 12 | Pages | e29017 |
| PubMed ID | 22194977 | Mgi Jnum | J:182352 |
| Mgi Id | MGI:5315249 | Doi | 10.1371/journal.pone.0029017 |
| Citation | De Paiva CS, et al. (2011) Disruption of TGF-beta signaling improves ocular surface epithelial disease in experimental autoimmune keratoconjunctivitis sicca. PLoS One 6(12):e29017 |
| abstractText | BACKGROUND: TGF-beta is a pleiotropic cytokine that can have pro- or anti-inflammatory effects depending on the context. Elevated levels of bioactive TGF-beta1 in tears and elevated TGF-beta1mRNA transcripts in conjunctiva and minor salivary glands of human Sjogren's Syndrome patients has also been reported. The purpose of this study was to evaluate the response to desiccating stress (DS), an experimental model of dry eye, in dominant-negative TGF-beta type II receptor (CD4-DNTGFbetaRII) mice. These mice have a truncated TGF-beta receptor in CD4(+) T cells, rendering them unresponsive to TGF-beta. METHODOLOGY/PRINCIPAL FINDINGS: DS was induced by subcutaneous injection of scopolamine and exposure to a drafty low humidity environment in CD4-DNTGFbetaRII and wild-type (WT) mice, aged 14 weeks, for 5 days. Nonstressed (NS) mice served as controls. Parameters of ocular surface disease included corneal smoothness, corneal barrier function and conjunctival goblet cell density. NS CD4-DNTGFbetaRII at 14 weeks of age mice exhibited a spontaneous dry eye phenotype; however, DS improved their corneal barrier function and corneal surface irregularity, increased their number of PAS+ GC, and lowered CD4(+) T cell infiltration in conjunctiva. In contrast to WT, CD4-DNTGFbetaRII mice did not generate a Th-17 and Th-1 response, and they failed to upregulate MMP-9, IL-23, IL-17A, RORgammaT, IFN-gamma and T-bet mRNA transcripts in conjunctiva. RAG1KO recipients of adoptively transferred CD4+T cells isolated from DS5 CD4-DNTGFbetaRII showed milder dry eye phenotype and less conjunctival inflammation than recipients of WT control. CONCLUSIONS/SIGNIFICANCE: Our results showed that disruption of TGF-beta signaling in CD4(+) T cells causes paradoxical improvement of dry eye disease in mice subjected to desiccating stress. |
