Critical Involvement of Macrophage Infiltration in the Development of Sjögren's Syndrome–Associated Dry Eye

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.

Is minor salivary gland biopsy more than a diagnostic tool in primary Sjo¨gren׳s syndrome? Association between clinical, histopathological, and molecular features: A retrospective study

“…T-cells predominate in mild lesions, whereas B-cells are the most represented cell subset in the advanced lesions, with a decrease in the percentage of macrophages and an increased percentage of DCs [14][15][16].…”

Innate immunity in Sjögren's syndrome

“…Of clinical importance, macrophages mediate dry eye in the Aire deficient mouse model for SS [66]. Notably, systemic macrophage depletion improves tear production in this model, demonstrating a definitive pathogenic role for these cells in disease [66].…”

Unmasking the pathogenic role of IL-17 axis in primary Sjögren's syndrome: A new era for therapeutic targeting?

“…The spectrum of minor salivary gland (MSG) histopathological damage ranges from mild infiltrates, where T-cells predominate, to diffuse infiltrates, with progressive loss of normal glandular tissue, where B-lymphocytes are the most represented cells [7][8][9].…”