IKZF1 Overexpression Is Associated with Inflammatory and ER Stress-Related Transcriptional Changes in Human Conjunctival Epithelial Cells

Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with severe ocular complications (SOCs) are devastating mucocutaneous disorders characterized by chronic ocular surface inflammation and epithelial damage. Although genome-wide association studies have identified IKZF1 as a susceptibility gene, its functional role in conjunctival epithelial cells remains unclear. Objective: This study aimed to characterize transcriptional changes and enrichment profiles associated with IKZF1 overexpression in primary human conjunctival epithelial cells. Methods: Primary human conjunctival epithelial cells (PHCjECs) were transfected with an IKZF1 expression plasmid or empty vector under matched transfection conditions, followed by microarray profiling, RT-qPCR validation, and Enrichr-based transcription factor enrichment analysis. Results: IKZF1 overexpression was associated with increased expression of CXCL8 and multiple stress-related transcripts, including DDIT3, and with enrichment of DDIT3-, ATF3-, and JUN-related transcriptional signatures. RT-qPCR confirmed significant induction of ER stress pathway genes, including ATF4, GRP78, and TRIB3. Furthermore, CHOP protein expression was markedly increased in conjunctival epithelium from patients with SJS/TEN compared with controls. Conclusions: IKZF1 overexpression is associated with inflammatory and stress-related transcriptional changes in conjunctival epithelial cells. These findings support a working hypothesis that epithelial IKZF1 upregulation may contribute to ocular surface pathology in SJS/TEN with severe ocular complications, but direct molecular mechanisms remain to be established.