Age-Dependent Distinct Distributions of Dendritic Cells in Autoimmune Dry Eye Murine Model

Abstract

We investigated whether aging-dependent changes in dendritic cell (DC) distributions are distinct in autoimmune dry eye compared with an aging-related murine model. Corneal staining and tear secretion were evaluated in young and aged C57BL/6 (B6) and NOD.B10.H2b mice (NOD). In the corneolimbus, lacrimal gland (LG), and mesenteric lymph node (MLN), CD11b− and CD11b+ DCs, CD103+ DCs and MHC-IIhi B cells were compared between young and aged B6 and NOD mice. With increased corneal staining, tear secretion decreased in both aged B6 and NOD mice (p < 0.001). In both aged B6 and NOD mice, the percentages of corneolimbal CD11b+ DCs were higher (p < 0.05) than those in young mice. While, the percentages of lymph nodal CD103+ DCs were higher in aged B6 and NOD mice (p < 0.05), the percentages of corneolimbal CD103+ DCs were only higher in aged NOD mice (p < 0.05). In aged NOD mice, the proportions of lacrimal glandial and lymph nodal MHC-IIhi B cells were also higher than those in young mice (p < 0.05). It indicates that corneolimbal or lacrimal glandial distribution of CD103+ DCs or MHC-IIhi B cells may be distinct in aged autoimmune dry eye models compared to those in aged immune competent murine models.

Neuroimmune crosstalk in the cornea: The role of immune cells in corneal nerve maintenance during homeostasis and inflammation

“…Aging can also affect immune cell phenotypes and their distribution at the ocular surface (Golebiowski et al, 2020;McClellan et al, 2014). In mice, a higher proportion of CD11b + CD11c + DCs was observed in aged mouse corneas compared to in younger eyes (Jung et al, 2021). Among the DC subtypes, CD11b-CD11c+ DCs induce cytotoxic CD8 + T cell and Th1 responses, while CD11b + CD11c + DCs initial Th17 and Treg responses (Sun et al, 2020).…”

The Molecular Mechanisms Responsible for Tear Hyperosmolarity-Induced Pathological Changes in the Eyes of Dry Eye Disease Patients

“…Antigens that bypass the THO-injured epithelial barrier are captured by skillful antigen-presenting DCs that reside in the corneal epithelium. THO induces an increased activation and maturation of DCs and promotes their recruitment in inflamed corneas and conjunctivas by enhancing the expression of adhesion molecules on epithelial and endothelial cells [50,51]. Accordingly, one study observed a significantly increased number of activated DCs in the ocular surfaces of THO mice compared to healthy controls (Figure 3) [51].…”

“…THO induces an increased activation and maturation of DCs and promotes their recruitment in inflamed corneas and conjunctivas by enhancing the expression of adhesion molecules on epithelial and endothelial cells [50,51]. Accordingly, one study observed a significantly increased number of activated DCs in the ocular surfaces of THO mice compared to healthy controls (Figure 3) [51]. Upon the engulfment of invading pathogens, activated DCs process their antigens and present them to naïve CD4+ T lymphocytes in regional lymph nodes.…”

Exploring Immune Cell Diversity in the Lacrimal Glands of Healthy Mice: A Single-Cell RNA-Sequencing Atlas

“…DCs, a diverse group of immune cells, play a critical role in antigen presentation and immune response regulation. These cells are present in various tissues, including lacrimal glands [11,133]. In our studies of mouse lacrimal glands, we first discovered the presence of predendritic cells (pre-DCs), which are the precursors of DCs.…”