REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1585528
This article is part of the Research TopicExploring KLF4's Role in Immune Cell Function and Disease ProgressionView all 5 articles
Alternative Splicing of KLF4 in Myeloid Cells: Implications for Cellular Plasticity and Trained Immunity in Cancer and Inflammatory Disease
Provisionally accepted
- 1Benedict College, Columbia, Missouri, United States
- 2School of Medicine Columbia, University of South Carolina, Columbia, South Carolina, United States
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The role of transcription factor Krüppel-like factor 4 (KLF4) in the modulation of myeloid cells is well known. KLF4 is involved in the differentiation and polarization of monocytes and macrophages as part of the immune response after infection, in wound healing, and in cancer. In addition, KLF4 is essential in stem cell reprogramming and the phenomenon of trained immunity -a form of innate immune memory marked by epigenetic and metabolic reprogramming. A novel and underexplored dimension of KLF4 biology lies in its alternative splicing (AS), which generates distinct isoforms that may drive the transcription factor's functions, depending on specific cellular environments, disease states, or signaling programs. This review presents current knowledge of KLF4 splicing in myeloid cells and explores novel connections for how KLF4 isoform diversity may contribute to cellular plasticity and differential immune responses of myeloid cells across physiological and pathological conditions.
Keywords: Krüppel-like factor 4 (KLF4), AS, Cellular plasticity, cancer stem cells, trained immunity, innate immunity, Myeloid-derived suppressor cells (MDSCs), epigenetics
Received: 28 Feb 2025; Accepted: 26 May 2025.
Copyright: © 2025 Shaw, Bennett, Fan and Ai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Walden Ai, Benedict College, Columbia, 29204, Missouri, United States
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