Title | Critical involvement of macrophage infiltration in the development of Sjögren's syndrome-associated dry eye. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Zhou D, Chen Y-T, Chen F, Gallup M, Vijmasi T, Bahrami AF, Noble LB, van Rooijen N, McNamara NA |
Journal | Am J Pathol |
Volume | 181 |
Issue | 3 |
Pagination | 753-60 |
Date Published | 2012 Sep |
ISSN | 1525-2191 |
Keywords | Adoptive Transfer, Animals, CD4-Positive T-Lymphocytes, Cell Movement, Clodronic Acid, Corneal Stroma, Dry Eye Syndromes, Eye, Humans, Limbus Corneae, Liposomes, Macrophages, Mice, Mice, Inbred BALB C, Mice, Inbred NOD, Mice, Knockout, Phenotype, Sjogren's Syndrome, Tears, Transcription Factors |
Abstract | Lymphocytic infiltration of the lacrimal gland and ocular surface in autoimmune diseases such as Sjögren's syndrome (SS) causes an aqueous-deficient dry eye that is associated with significant morbidity. Previous studies from our laboratory and others have established autoimmune regulator (Aire)-deficient mice as a useful model to examine exocrinopathy and ocular surface disease associated with SS. Consistent with human SS, autoreactive CD4(+) T cells play an indispensible role in the development of exocrine and ocular surface disease in Aire knockout mice. We report that in addition to CD4(+) T cells, a large number of macrophages infiltrate the corneal stroma, limbus, and lacrimal glands of diseased mice. Adoptive transfer of autoreactive CD4(+) T cells from Aire knockout mice led to local infiltration of macrophages and ocular surface damage in immunodeficient recipients. Depletion of local macrophages, through subconjunctival injection of clodronate liposome, attenuated lissamine green staining and improved ocular phenotype. Alternatively, systemic depletion of macrophages had no effect on ocular phenotype but led to significant improvements in lacrimal gland exocrinopathy and tear secretion. Our results suggested that autoreactive CD4(+) T cells provoked macrophage infiltration to the eye and lacrimal gland, where they played a functional role in directing the development of autoimmune dry eye. |
DOI | 10.1016/j.ajpath.2012.05.014 |
Alternate Journal | Am. J. Pathol. |
PubMed ID | 22770665 |
PubMed Central ID | PMC3432423 |
Grant List | P30 EY002162 / EY / NEI NIH HHS / United States R01 EY016203 / EY / NEI NIH HHS / United States EY016203 / EY / NEI NIH HHS / United States EY02162 / EY / NEI NIH HHS / United States |
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