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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