Uveitis-mediated immune cell invasion through the extracellular matrix of the lens capsule

Authors

JodiRae DeDreu, Department of Pathology, Anatomy and Cell Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Sonali Pal-Ghosh, Department of Anatomy and Cell Biology, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Mary J. Mattapallil, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Rachel R. Caspi, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Mary Ann Stepp, Department of Anatomy and Cell Biology, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
A Sue Menko, Department of Pathology, Anatomy and Cell Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Document Type

Journal Article

Publication Date

1-1-2022

Journal

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Volume

36

Issue

1

DOI

10.1096/fj.202101098R

Keywords

basement membrane; immune cell attachment; immune cell infiltration; immune cell migration; immune privilege; inflammation; lens; matrix; uveitic

Abstract

While the eye is considered an immune privileged site, its privilege is abrogated when immune cells are recruited from the surrounding vasculature in response to trauma, infection, aging, and autoimmune diseases like uveitis. Here, we investigate whether in uveitis immune cells become associated with the lens capsule and compromise its privilege in studies of C57BL/6J mice with experimental autoimmune uveitis. These studies show that at D14, the peak of uveitis in these mice, T cells, macrophages, and Ly6G/Ly6C+ immune cells associate with the lens basement membrane capsule, burrow into the capsule matrix, and remain integrated with the capsule as immune resolution is occurring at D26. 3D surface rendering image analytics of confocal z-stacks and scanning electron microscopy imaging of the lens surface show the degradation of the lens capsule as these lens-associated immune cells integrate with and invade the lens capsule, with a subset infiltrating both epithelial and fiber cell regions of lens tissue, abrogating its immune privilege. Those immune cells that remain on the surface often become entwined with a fibrillar net-like structure. Immune cell invasion of the lens capsule in uveitis has not been described previously and may play a role in induction of lens and other eye pathologies associated with autoimmunity.

APA Citation

DeDreu, JodiRae; Pal-Ghosh, Sonali; Mattapallil, Mary J.; Caspi, Rachel R.; Stepp, Mary Ann; and Menko, A Sue, "Uveitis-mediated immune cell invasion through the extracellular matrix of the lens capsule" (2022). GW Authored Works. Paper 447.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/447

Department

Anatomy and Regenerative Biology