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. 2022 Aug 24;15(6):1143–1157. doi: 10.1038/s41385-022-00551-6

Fig. 4. The immune response in dry eye disease and the vicious cycle of inflammation.

Fig. 4

Homeostasis: 1-In homeostasis, the ocular surface is paucibacterial and has innumerous anti-microbial defenses, including a healthy tear film rich in anti-microbial proteins (SA100s, lysozyme). In the conjunctiva, goblet cells secrete retinoic acid (RA) and TGF-beta that maintain the resident dendritic cells in an immature state. 2- Immature dendritic cells provide ocular surveillance and migrate constantly to the ocular draining nodes where regulatory T cells (Tregs) are preferentially primed. dry eye disease: 1-Insults to the ocular surface cause activation of epithelial cells, disrupted tear film and glycocalyx which in turn lead to secretion of chemokines, secretion of T helper (Th) polarizing cytokines such as IL-12 and IL-23 and upregulation of CD86 and MHC II, leading to activated dendritic cells. Loss of goblet cells and squamous metaplasia of the conjunctival epithelium lead to goblet cells that do not properly secrete at the ocular surface. Secondary to loss of goblet cells, there is less RA and TGF-β, leading to further APC activation. 2-Activated dendritic cells migrate to ocular lymph nodes. 3-Mature dendritic cells primer naïve T cells into Th1 and Th17 cells. 4-Activated Th1 and Th17 cells migrate back to the eye, where they secrete IFN-γ and IL-17, which cause goblet cell loss, corneal barrier disruption and activation of innate immunity. Dysfunctional Tregs also participate in the immune response of dry eye disease (not despicted). 5- Insults to the ocular surface reinitiate the vicious cycle of dry eye activating epithelial cells, disrupting the tear film and glycocalyx which in turn lead to secretion of chemokines, secretion of Th polarizing cytokines such as IL-12 and IL-23 and upregulation of CD86 and MHC II, leading to activated dendritic cells. Loss of goblet cells and squamous metaplasia of the conjunctival epithelium lead to goblet cells that do not properly secrete at the ocular surface. Secondary to loss of goblet cells, there is less RA and TGF-β, leading to further APC activation.