TY - JOUR
T1 - Immunologic basis for development of keratoconjunctivitis sicca in systemic autoimmune diseases
T2 - Role of innate immune sensors
AU - Stern, Michael E.
AU - Theofilopoulos, Argyrios N.
AU - Steven, Philipp
AU - Niederkorn, Jerry Y.
AU - Fox, Robert
AU - Calonge, Margarita
AU - Scheid, Christof
AU - Pflugfelder, Stephen C.
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/4
Y1 - 2024/4
N2 - The literature is filled with citations reporting an increased incidence of chronic dry eye disease, also known as keratoconjunctivitis sicca, in patients with systemic autoimmune diseases such as rheumatoid arthritis, Sjögren's Syndrome, systemic sclerosis and lupus. As the most environmentally exposed mucosal surface of the body, the conjunctiva constantly responds to environmental challenges which are typically self limited, but when persistent and unresolved may provoke pathogenic innate and adaptive immune reactions. Our understanding of the pathophysiological mechanisms by which systemic autoimmune diseases cause dry eye inducing ocular surface inflammation continues to evolve. Conjunctival immune tone responds to self or foreign danger signals (including desiccating stress) on the ocular surface with an initial non-specific innate inflammatory response. If unchecked, this can lead to activation of dendritic cells that present antigen and prime T and B cells resulting in an adaptive immune reaction. These reactions generally resolve, but dysfunctional, hyper-responsive immune cells found in systemic autoimmune diseases that are recruited to the ocular surface can amplify inflammatory stress responses in the ocular surface and glandular tissues and result in autoimmune reactions that disrupt tear stability and lead to chronic dry eye disease. We here propose that unique features of the ocular surface immune system and the impact of systemic immune dysregulation in autoimmune diseases, can predispose to development of dry eye disease, and exacerbate severity of existing dry eye.
AB - The literature is filled with citations reporting an increased incidence of chronic dry eye disease, also known as keratoconjunctivitis sicca, in patients with systemic autoimmune diseases such as rheumatoid arthritis, Sjögren's Syndrome, systemic sclerosis and lupus. As the most environmentally exposed mucosal surface of the body, the conjunctiva constantly responds to environmental challenges which are typically self limited, but when persistent and unresolved may provoke pathogenic innate and adaptive immune reactions. Our understanding of the pathophysiological mechanisms by which systemic autoimmune diseases cause dry eye inducing ocular surface inflammation continues to evolve. Conjunctival immune tone responds to self or foreign danger signals (including desiccating stress) on the ocular surface with an initial non-specific innate inflammatory response. If unchecked, this can lead to activation of dendritic cells that present antigen and prime T and B cells resulting in an adaptive immune reaction. These reactions generally resolve, but dysfunctional, hyper-responsive immune cells found in systemic autoimmune diseases that are recruited to the ocular surface can amplify inflammatory stress responses in the ocular surface and glandular tissues and result in autoimmune reactions that disrupt tear stability and lead to chronic dry eye disease. We here propose that unique features of the ocular surface immune system and the impact of systemic immune dysregulation in autoimmune diseases, can predispose to development of dry eye disease, and exacerbate severity of existing dry eye.
KW - Autoimmunity
KW - Dry eye
KW - Immune tone
KW - Innate immunity
KW - Keratoconjunctivitis sicca
UR - http://www.scopus.com/inward/record.url?scp=85187019126&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85187019126&partnerID=8YFLogxK
U2 - 10.1016/j.jtos.2024.02.003
DO - 10.1016/j.jtos.2024.02.003
M3 - Article
C2 - 38395195
AN - SCOPUS:85187019126
SN - 1542-0124
VL - 32
SP - 130
EP - 138
JO - Ocular Surface
JF - Ocular Surface
ER -