Activation of Dendritic Cells in Dry Eye Mouse Model

Invest Ophthalmol Vis Sci. 2018 Jul 2;59(8):3269-3277. doi: 10.1167/iovs.17-22550.

Abstract

Purpose: The immune system plays a major role in the pathogenesis of dry eye diseases (DED), and dendritic cells (DCs) are known to be important initiators of acquired immunity. Thus, the purpose of this study was to determine the contribution of DCs to the development of DED.

Methods: Mouse dry eye model was induced by subcutaneous injections of scopolamine and was euthanized at the baseline, and 2, 4, and 7 days postinjection. The activation of the DCs was determined by the mixed leukocyte reaction (MLR), and the number of activated CD86+ DCs in the lymph nodes was determined by flow cytometry. Upregulation of cytokines in the culture supernatant of MLR was determined by ELISA.

Results: Significantly increased superficial corneal punctate lesions and decreased number of goblet cells in the conjunctiva were observed in scopolamine-injected mice. The number of activated CD86+ DCs was significantly increased in the cervical lymph nodes but not in the inguinal lymph nodes of the dry eye mice. The stimulatory activity of the DCs derived from the cervical lymph nodes of dry eye mice was significantly higher than that of control mice, and upregulations of IL-17, IL-2, and IL-4 were observed in the culture supernatant of MLR. These results indicate that the DCs of the cervical lymph nodes were activated by the scopolamine injections.

Conclusions: Our results indicate that DCs in our dry eye model were sufficiently activated to stimulate the T cells that participate in the onset and progression of DED.

MeSH terms

  • Animals
  • B7-2 Antigen / metabolism
  • Biomarkers / metabolism
  • Cornea / metabolism*
  • Cornea / pathology
  • Cytokines / metabolism
  • Dendritic Cells / physiology*
  • Disease Models, Animal*
  • Dry Eye Syndromes / etiology*
  • Dry Eye Syndromes / metabolism
  • Dry Eye Syndromes / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Goblet Cells / pathology
  • Lymph Nodes / metabolism
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Mice, Inbred C57BL
  • Mydriatics / pharmacology
  • Scopolamine / pharmacology

Substances

  • B7-2 Antigen
  • Biomarkers
  • Cd86 protein, mouse
  • Cytokines
  • Mydriatics
  • Scopolamine