TSLP and downstream molecules in experimental mouse allergic conjunctivitis

Invest Ophthalmol Vis Sci. 2010 Jun;51(6):3076-82. doi: 10.1167/iovs.09-4122. Epub 2010 Jan 27.

Abstract

Purpose: To explore the potential role of thymic stromal lymphopoietin (TSLP) and its downstream molecules in the development of ocular allergic inflammation using a short ragweed (SRW)-induced mouse model of allergic conjunctivitis (AC).

Methods: BALB/c mice were topically challenged with SRW pollen after they were sensitized with SRW in the footpad. After the last SRW challenge, the corneal epithelium, conjunctiva, and cervical lymph nodes were harvested for total RNA extraction and gene expression by RT and real-time PCR, and whole eye globes were collected to make cryosections for immunohistochemical staining.

Results: Repeated topical challenges with SRW allergen generated typical signs of AC in mice. Compared with the untreated controls, TSLP mRNA expression and immunoreactivity were significantly increased in the corneal and conjunctival epithelia of SRW-induced AC mice. CD11c(+) and OX40L(+) immunoreactive cells largely infiltrated the conjunctiva with increased mRNA levels of CD11c, TSLPR, and OX40L detected in the corneal epithelium, conjunctiva, and cervical lymph nodes. CD4(+) Th2 cell infiltration was evidenced by increased levels of mRNA and immunoreactivity of CD4, IL-4, IL-5, and IL-13 in the ocular surface, mainly in the conjunctiva, accompanied by increased expression of OX40, STAT6, and GATA3, in AC mice. The maturation of immature DCs was observed with the use of TSLP containing conditioned media from corneal epithelial cultures exposed to polyI:C, which stimulates TSLP production.

Conclusions: This study provides new findings regarding the role of local mucosal epithelial cells in the initiation of ocular allergic inflammation by producing a novel proallergic cytokine, TSLP, which activates dendritic cells to prime Th2 differentiation and allergic inflammation through the TSLP-TSLPR and OX40L-OX40 signaling pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens
  • Animals
  • Antigens, Plant
  • Conjunctiva / immunology
  • Conjunctivitis, Allergic / immunology*
  • Cytokines / genetics*
  • Dendritic Cells / immunology
  • Disease Models, Animal*
  • Epithelium, Corneal / immunology
  • Female
  • Gene Expression Regulation / physiology*
  • Immunoenzyme Techniques
  • Immunoglobulins
  • Lymph Nodes / immunology
  • Lymphocyte Activation
  • Male
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • OX40 Ligand
  • Plant Proteins
  • Pollen
  • RNA, Messenger / metabolism
  • Receptors, Cytokine / metabolism
  • Receptors, OX40 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Th2 Cells / immunology
  • Tumor Necrosis Factors / metabolism

Substances

  • Allergens
  • Amb a I protein, Ambrosia artemisiifolia
  • Antigens, Plant
  • Cytokines
  • Immunoglobulins
  • Membrane Glycoproteins
  • OX40 Ligand
  • Plant Proteins
  • RNA, Messenger
  • Receptors, Cytokine
  • Receptors, OX40
  • Tnfrsf4 protein, mouse
  • Tnfsf4 protein, mouse
  • Tslpr protein, mouse
  • Tumor Necrosis Factors
  • thymic stromal lymphopoietin