July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Interleukin-23 is Essential for Development of Pathogenic Memory T Helper-17 Cells in Chronic Dry Eye Disease
Author Affiliations & Notes
  • Yihe Chen
    Schepens Eye Research Ins /MEEI, Boston, Massachusetts, United States
  • Chunyi Shao
    Schepens Eye Research Ins /MEEI, Boston, Massachusetts, United States
  • Takeshi Nakao
    Schepens Eye Research Ins /MEEI, Boston, Massachusetts, United States
  • Sunil Chauhan
    Schepens Eye Research Ins /MEEI, Boston, Massachusetts, United States
  • Reza Dana
    Schepens Eye Research Ins /MEEI, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Yihe Chen, None; Chunyi Shao, None; Takeshi Nakao, None; Sunil Chauhan, None; Reza Dana, None
  • Footnotes
    Support  NIH R01 EY 20889
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2554. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Yihe Chen, Chunyi Shao, Takeshi Nakao, Sunil Chauhan, Reza Dana; Interleukin-23 is Essential for Development of Pathogenic Memory T Helper-17 Cells in Chronic Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2554.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Following the progression of dry eye disease (DED) to the chronic phase, the predominant effector T helper (Th) 17 cells switch to long-term surviving memory Th17 (mTh17) cells. We have shown that these mTh17 cells are primarily responsible for sustaining chronic inflammation in DED, and are maintained by interleukin (IL)-7 and IL-15. However, it is unknown how these mTh17 cells are developed from their effector precursors. This study investigated the requirement for IL-23 and IL-2 signaling in the development of mTh17 cells in a mouse model of DED.

Methods : Acute DED was induced by exposing C57BL/6 mice to environmental desiccating stress for 14 days. Effector T cells (CD62L-CD44loCD4+) from the draining lymph nodes of acute DED mice were isolated using FACS sorting, and cultured in the presence of IL-23 (10ng/mL), IL-2 (50IU/mL), CD25 blocking antibody (mAb) (10μg/mL), IL-23+IL-2, or IL-23+CD25 mAb for 48 hours. The frequencies of mTh17 cells (CD44hiIL-17A+CD4+), expression levels of IL-7 and IL-15 receptors, as well as Annexin V and Ki-67 by Th17 cells were then assessed using flow cytometry. Furthermore, IL-23 signaling was blocked by intraperitoneal injection of anti-IL-23R Ab at day 14 when acute DED mice were returned to the normal environment. The disease severity was then evaluated for 7 days by corneal fluorescein staining (CFS), and mTh17 cells were examined using flow cytometry.

Results : After 48 hours of culture of DED effector T cells, the frequencies of generated mTh17 cells were significantly higher in the presence of IL-23 (54±3%; p < 0.001), CD25 mAb (35±1%; p < 0.001), or IL-23+CD25 mAb (65±1%; p < 0.001) than those cultured in the media alone (23±1%). In addition, IL-23, CD25 mAb, and IL-23+CD25 mAb all dramatically enhanced the expression of IL-15R (MFI = 85, 64, 97 respectively vs. 8 in media alone), while suppressing Annexin V expression by Th17 cells (MFI = 70, 67, 23 respectively vs. 134 in media alone). In vivo blockade of IL-23 signaling prevented the development of mTh17 cells from existing effector Th17 cells by 30% (p = 0.019), and significantly decreased ongoing disease severity by 33% (p = 0.004).

Conclusions : IL-23 is required for the development of pathogenic memory Th17 cells in chronic DED by up-regulating IL-15 receptor expression and preventing apoptosis of Th17 cells.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×