PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Mucosal Immunol. Author manuscript; available in PMC 2010 July 1.
Published in final edited form as:
PMCID: PMC2719854
NIHMSID: NIHMS125465

Role of Th17 Cells in the Immunopathogenesis of Dry Eye Disease

Letter

The article by De Paiva et al.1 provides additional evidence that interleukin-17 (IL-17) is associated with disruption of corneal epithelial barrier function, which is the most sight-threatening complication of dry eye disease (DE), arguably the most common ophthalmologic condition. It reports increased expression of Th17 cell inducers including IL-6, TGF-β, IL-23 and IL-17A on the ocular surface of DE patients as well as increased concentration of IL-17 in tears and number of Th17 cells on the ocular surface of experimental animals with DE. In addition, authors show that IL-17 induced secretion of MMP-3 and -9 by epithelial cells causes a significant increase in corneal epithelial permeability which is ameliorated by in-vivo neutralization of IL-17.

However, the precise etiopathogenesis of DE, particularly the nature of ocular surface autoantigen(s), and the site and mechanism of generation of these self-reactive T cells is still not very clear24. In a recent article5, we have demonstrated not only the involvement of Th17 cells in dry eye pathogenesis but also the mechanism of induction of autoimmunity in the draining lymph nodes (LN) using a mouse model of DE. In addition to the expression of Th17 profile on the ocular surface, we showed increased frequency of Th17 cells in the draining LN where these cells exhibit specific resistance to regulatory-T cell (Treg) mediated suppression. In agreement with De Pavia et al.1, the functional relevance of Th17 cells in the pathogenesis of DE was fundamentally confirmed by demonstrating that in-vivo neutralization of IL-17 results in a markedly attenuated induction and severity of disease. Interestingly, DE amelioration was paralleled by a reduction in the expansion of Th17 cells and prevention of the loss of Treg function in the draining LN suggesting that Th17 cell-secreted-IL-17 antagonizes the Treg function, which in turn further unleashes Th17 and Th1 cells to expand, migrate to ocular surface and cause epithelial damage. Together, these studies suggest that Th17 cells are the dominant pathogenic effectors in DE. Based on current1,2 and previously published35 data, an overarching hypothesis of the mechanism(s) involved in the pathogenesis of DE is illustrated in Figure-1. DE affects visual performance and the quality of life of >10 million people in the United States alone. The current demonstration that IL-17 blockade leads to diminished disease severity suggests potential novel approaches for the treatment of DE.

Figure 1
Immunopathogenesis of dry eye disease

ACKNOWLEDGEMENTS

This work was supported in part by National Institutes of Health Grant NEI R01-12963.

REFERENCES

1. De Paiva CS, Chotikavanich S, Pangelinan SB, Pitcher JD, III, Fang B, Zheng X, Ma P, Farley WJ, Siemasko KF, Niederkorn JY, Stern ME, Li DQ, Pflugfelder SC. IL-17 disrupts corneal barrier following desiccating stress. Mucosal. Immunol. 2009;2:243–253. [PMC free article] [PubMed]
2. Pflugfelder SC, de Paiva CS, Li DQ, Stern ME. Epithelial-immune cell interaction in dry eye. Cornea. 2008;27 Suppl 1:S9–S11. [PMC free article] [PubMed]
3. Report of the International Dry Eye WorkShop. Ocul. Surf. 2007;5:179–193. No authors listed. [PubMed]
4. Barabino S, Dana MR. Dry eye syndromes. Chem. Immunol. Allergy. 2007;92:176–184. [PubMed]
5. Chauhan SK, El Annan J, Ecoiffier T, Goyal S, Zhang Q, Saban DR, Dana R. Autoimmunity in dry eye is due to resistance of Th17 to Treg suppression. J. Immunol. 2009;182:1247–1252. [PMC free article] [PubMed]