Lacrimal gland-derived IL-22 regulates IL-17-mediated ocular mucosal inflammation

Y. W. Ji, S. K. Mittal, H. S. Hwang, E. J. Chang, J. H. Lee, KyoungYul Seo, A. Yeo, H. Noh, H. S. Lee, S. K. Chauhan, H. K. Lee

Research output: Contribution to journalArticle

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Abstract

Inflammatory damage of mucosal surface of the eye is a hallmark of dry eye disease (DED) and, in severe cases, can lead to significant discomfort, visual impairment, and blindness. DED is a multifactorial autoimmune disorder with a largely unknown pathogenesis. Using a cross-sectional patient study and a well-characterized murine model of DED, herein we investigated the immunoregulatory function of interleukin-22 (IL-22) in the pathogenesis of DED. We found that IL-22 levels were elevated in lacrimal fluids of DED patients and inversely correlated with severity of disease. Acinar cells of the lacrimal glands (LGs), not inflammatory immune cells, are the primary source of IL-22, which suppresses inflammation in ocular surface epithelial cells upon desiccating stress. Moreover, loss of function analyses using IL-22 knockout mice demonstrated that IL-22 is essential for suppression of ocular surface infiltration of Th17 cells and inhibition of DED induction. Our novel findings elucidate immunoregulatory function of LG-derived IL-22 in inhibiting IL-17-mediated ocular surface epitheliopathy in DED thus making IL-22 a new relevant therapeutic target.

Original languageEnglish
Pages (from-to)1202-1210
Number of pages9
JournalMucosal Immunology
Volume10
Issue number5
DOIs
Publication statusPublished - 2017 Sep 1

Fingerprint

Lacrimal Apparatus
Interleukin-17
Eye Diseases
Inflammation
Th17 Cells
Acinar Cells
Vision Disorders
Blindness
interleukin-22
Tears
Knockout Mice
Cross-Sectional Studies
Epithelial Cells

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Ji, Y. W., Mittal, S. K., Hwang, H. S., Chang, E. J., Lee, J. H., Seo, K., ... Lee, H. K. (2017). Lacrimal gland-derived IL-22 regulates IL-17-mediated ocular mucosal inflammation. Mucosal Immunology, 10(5), 1202-1210. https://doi.org/10.1038/mi.2016.119
Ji, Y. W. ; Mittal, S. K. ; Hwang, H. S. ; Chang, E. J. ; Lee, J. H. ; Seo, KyoungYul ; Yeo, A. ; Noh, H. ; Lee, H. S. ; Chauhan, S. K. ; Lee, H. K. / Lacrimal gland-derived IL-22 regulates IL-17-mediated ocular mucosal inflammation. In: Mucosal Immunology. 2017 ; Vol. 10, No. 5. pp. 1202-1210.
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Ji, YW, Mittal, SK, Hwang, HS, Chang, EJ, Lee, JH, Seo, K, Yeo, A, Noh, H, Lee, HS, Chauhan, SK & Lee, HK 2017, 'Lacrimal gland-derived IL-22 regulates IL-17-mediated ocular mucosal inflammation', Mucosal Immunology, vol. 10, no. 5, pp. 1202-1210. https://doi.org/10.1038/mi.2016.119

Lacrimal gland-derived IL-22 regulates IL-17-mediated ocular mucosal inflammation. / Ji, Y. W.; Mittal, S. K.; Hwang, H. S.; Chang, E. J.; Lee, J. H.; Seo, KyoungYul; Yeo, A.; Noh, H.; Lee, H. S.; Chauhan, S. K.; Lee, H. K.

In: Mucosal Immunology, Vol. 10, No. 5, 01.09.2017, p. 1202-1210.

Research output: Contribution to journalArticle

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AU - Ji, Y. W.

AU - Mittal, S. K.

AU - Hwang, H. S.

AU - Chang, E. J.

AU - Lee, J. H.

AU - Seo, KyoungYul

AU - Yeo, A.

AU - Noh, H.

AU - Lee, H. S.

AU - Chauhan, S. K.

AU - Lee, H. K.

PY - 2017/9/1

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N2 - Inflammatory damage of mucosal surface of the eye is a hallmark of dry eye disease (DED) and, in severe cases, can lead to significant discomfort, visual impairment, and blindness. DED is a multifactorial autoimmune disorder with a largely unknown pathogenesis. Using a cross-sectional patient study and a well-characterized murine model of DED, herein we investigated the immunoregulatory function of interleukin-22 (IL-22) in the pathogenesis of DED. We found that IL-22 levels were elevated in lacrimal fluids of DED patients and inversely correlated with severity of disease. Acinar cells of the lacrimal glands (LGs), not inflammatory immune cells, are the primary source of IL-22, which suppresses inflammation in ocular surface epithelial cells upon desiccating stress. Moreover, loss of function analyses using IL-22 knockout mice demonstrated that IL-22 is essential for suppression of ocular surface infiltration of Th17 cells and inhibition of DED induction. Our novel findings elucidate immunoregulatory function of LG-derived IL-22 in inhibiting IL-17-mediated ocular surface epitheliopathy in DED thus making IL-22 a new relevant therapeutic target.

AB - Inflammatory damage of mucosal surface of the eye is a hallmark of dry eye disease (DED) and, in severe cases, can lead to significant discomfort, visual impairment, and blindness. DED is a multifactorial autoimmune disorder with a largely unknown pathogenesis. Using a cross-sectional patient study and a well-characterized murine model of DED, herein we investigated the immunoregulatory function of interleukin-22 (IL-22) in the pathogenesis of DED. We found that IL-22 levels were elevated in lacrimal fluids of DED patients and inversely correlated with severity of disease. Acinar cells of the lacrimal glands (LGs), not inflammatory immune cells, are the primary source of IL-22, which suppresses inflammation in ocular surface epithelial cells upon desiccating stress. Moreover, loss of function analyses using IL-22 knockout mice demonstrated that IL-22 is essential for suppression of ocular surface infiltration of Th17 cells and inhibition of DED induction. Our novel findings elucidate immunoregulatory function of LG-derived IL-22 in inhibiting IL-17-mediated ocular surface epitheliopathy in DED thus making IL-22 a new relevant therapeutic target.

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