Purchase this article with an account.
Yihe Chen, Chunyi Shao, Takeshi Nakao, Sunil Chauhan, Reza Dana; Interleukin-23 is Required for the In Vivo Generation of Memory T Helper-17 Cells. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6726.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Memory T helper-17 (mTh17) cells have been detected in various human immunoinflammatory disorders, and we have demonstrated that mTh17 cells are critical in maintaining chronic ocular surface inflammation in a preclinical model of autoimmune dry eye disease (DED). We have further shown that ex vivo culture of DED effector Th17 cells in the presence of interlukin-23 (IL-23) leads to significant conversion of those effectors to memory Th17 cells. Here we have investigated the role of IL-23 in the in vivo development of mTh17.
DED was induced by exposing congenic CD45.1 and CD45.2 C57BL/6 mice to environmental desiccating stress for 14 days. Effector Th cells (CD62L-CD44loCD4+) from the draining lymph nodes (DLNs) of CD45.2 DED mice were isolated using FACS sorting. Approximately 1×106 effector cells were then intravenously transferred to congenic CD45.1 DED mice that received an intraperitoneal injection of anti-IL-23R Ab or isotype IgG (control). The recipient mice were immediately returned to the normal environment. CD45.1 DED mice without cell transfer served as an additional control. After 7 days, the DLNs and conjunctiva of the donor (CD45.2+) effector Th cell were collected and the number of CD45.2+ mTh17 cells (CD44hiIL-7R+IL-17A+CD4+) in DLNs and conjunctiva were examined using flow cytometry.
In the control recipients, CD45.2+ cells could be detected in both DLN and conjunctival tissue. In the anti-IL-23R Ab-treated recipients, the total number of CD45.2+ cells detected in the DLNs (~ 200 cells out of 2×105 total cells) was not significantly different compared to control recipients, however treatment did decrease the number of CD45.2+ cells in the conjunctiva (~ 15 out of 3.5×104). Among total CD45.2+ cells, the frequency of CD45.2+ Th17 cells did not significantly change in DLNs (control: 12.0±0.6% vs. Ab: 13.0±0.5%), but was abolished in the conjunctiva following anti-IL-23R Ab treatment (control: 12.9% vs. Ab: 0). Despite the similar frequency of total CD45.2+ Th17 in DLNs, the fraction of CD45.2+ mTh17 was significantly diminished by the anti-IL-23R Ab treatment (control: 82.9±0.9% vs. Ab: 65.2±1.5%, p < 0.05). In the conjunctiva of control recipients, 75% of CD45.2+ Th17 cells are CD44hiIL-7R+ mTh17 cells.
Our results suggest that IL-23 is required for the in vivo development of memory Th17 cells from their effector precursors.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
This PDF is available to Subscribers Only