1. Academic Validation
  2. SHIP-1 affects herpetic simplex keratitis prognosis by mediating CD4+ T lymphocytes migration through PI3K signaling and transcription factor KLF2 in the cornea

SHIP-1 affects herpetic simplex keratitis prognosis by mediating CD4+ T lymphocytes migration through PI3K signaling and transcription factor KLF2 in the cornea

  • Antiviral Res. 2022 Sep 22;207:105424. doi: 10.1016/j.antiviral.2022.105424.
Qiyu Qin 1 Yi Wang 1 Xiaodan Huang 1 Xiuming Jin 2
Affiliations

Affiliations

  • 1 Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University No.1 Xihu Boulevard, Hangzhou, 310009, China.
  • 2 Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University No.1 Xihu Boulevard, Hangzhou, 310009, China. Electronic address: lzyjxm@zju.edu.cn.
Abstract

Herpetic simplex keratitis (HSK) mainly represents an immune cell-mediated, and more specifically, CD4+ T cell-orchestrated inflammatory response to virus invasion. The virus in infected corneas could be easily inhibited or hidden in the trigeminal ganglion using Antiviral drugs, but the immune-related inflammation will last for a long time and lead to significant complications. In the present study, we found that the subconjunctival injection of SHIP-1 activator AQX1125 in mouse HSK model alleviated the corneal inflammatory and angiogenic responses, as well as promoted quicker recovery of the cornea, with significantly fewer infiltration of CD4+ T lymphocytes. Furthermore, using primary CD4+ T lymphocytes, we observed that by modulating PI3K signaling and the expression of transcription factors KLF2 and CCR7, SHIP-1 could significantly influence the migration of lymphocytes toward CCL19 and 21, which are the "exit cues" for cells to emigrate from inflammatory sites. Thus, we propose that the pharmacological SHIP-1 activation represents a new potential therapeutic approach to control HSK lesions, and its function on the CCR7-CCL19/21 biological axis may be a novel underlying mechanism for its anti-inflammatory action.

Keywords

21; CCL19; CCR7; CD4(+) T lymphocytes; Herpetic simplex keratitis; SHIP-1.

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