Conditional deletion of Zeb1 in Csf1r+ cells reduces inflammatory response of the cornea to alkali burn

Khoi K Do; Fuhua Wang; Xiaolei Sun; Yingnan Zhang; Wei Liang; John Y Liu; Daniel Y Jiang; Xiaoqin Lu; Wei Wang; Lijun Zhang; Douglas C Dean; Yongqing Liu

doi:10.1016/j.isci.2024.109694

Conditional deletion of Zeb1 in Csf1r⁺ cells reduces inflammatory response of the cornea to alkali burn

iScience. 2024 Apr 9;27(5):109694. doi: 10.1016/j.isci.2024.109694. eCollection 2024 May 17.

Authors

Khoi K Do¹, Fuhua Wang^{1

2}, Xiaolei Sun^{1

2}, Yingnan Zhang^{1

3}, Wei Liang^{1

4}, John Y Liu¹, Daniel Y Jiang¹, Xiaoqin Lu¹, Wei Wang⁵, Lijun Zhang⁴, Douglas C Dean^{1

5

6}, Yongqing Liu^{1

5

6}

Affiliations

¹ Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.
² Eye Institute and Eye Hospital of Shangdong First Medical University, Jinan 250021, China.
³ The Rosenberg School of Optometry, University of the Incarnate Word, San Antonio, TX 78229, USA.
⁴ Department of Ophthalmology, Third People's Hospital of Dalian, Dalian Medical University, Dalian 116033, China.
⁵ Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, KY 40202, USA.
⁶ James Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.

Abstract

ZEB1 is an essential factor in embryonic development. In adults, it is often highly expressed in malignant tumors with low expression in normal tissues. The major biological function of ZEB1 in developing embryos and progressing cancers is to transdifferentiate cells from an epithelial to mesenchymal phenotype; but what roles ZEB1 plays in normal adult tissues are largely unknown. We previously reported that the reduction of Zeb1 in monoallelic global knockout (Zeb1^+/-) mice reduced corneal inflammation-associated neovascularization following alkali burn. To uncover the cellular mechanism underlying the Zeb1 regulation of corneal inflammation, we functionally deleted Zeb1 alleles in Csf1r⁺ myeloid cells using a conditional knockout (cKO) strategy and found that Zeb1 cKO reduced leukocytes in the cornea after alkali burn. The reduction of immune cells was due to their increased apoptotic rate and linked to a Zeb1-downregulated apoptotic pathway. We conclude that Zeb1 facilitates corneal inflammatory response by maintaining Csf1r⁺ cell viability.

Keywords: Immunology; Ophthalmology.