The role of KLF4 in phagocyte activation during infectious diseases

Phagocytes, including granulocytes (especially neutrophils), monocytes, macrophages, and dendritic cells, are essential components of the innate immune system, bridging innate and adaptive immunity. Their activation and function are tightly regulated by transcription factors that coordinate immune r...

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Main Authors: Toni Herta, Aritra Bhattacharyya, Stefan Hippenstiel, Janine Zahlten
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1584873/full
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author Toni Herta
Toni Herta
Aritra Bhattacharyya
Stefan Hippenstiel
Janine Zahlten
author_facet Toni Herta
Toni Herta
Aritra Bhattacharyya
Stefan Hippenstiel
Janine Zahlten
author_sort Toni Herta
collection DOAJ
description Phagocytes, including granulocytes (especially neutrophils), monocytes, macrophages, and dendritic cells, are essential components of the innate immune system, bridging innate and adaptive immunity. Their activation and function are tightly regulated by transcription factors that coordinate immune responses. Among these, Krüppel-like factor 4 (KLF4) has gained attention as a regulator of phagocyte differentiation, polarization, and inflammatory modulation. However, its role is highly context-dependent, exhibiting both pro- and anti-inflammatory properties based on environmental signals, cellular states, and the invading pathogen. KLF4 influences monocyte-to-macrophage differentiation and shapes macrophage polarization, promoting either inflammatory or regulatory phenotypes depending on external cues. In neutrophils, it affects reactive oxygen species production and immune activation, while in dendritic cells, it regulates monocyte-to-dendritic cell differentiation and cytokine secretion. Its diverse involvements in immune responses suggests that it contributes to maintaining a balance between effective pathogen defense and the prevention of excessive and potentially harmful inflammation. This review summarizes current knowledge on the function of KLF4 in phagocytes during infections, highlighting its regulatory mechanisms, context-dependent roles, and its impact on immune activation and resolution. Additionally, potential implications for therapeutic interventions targeting KLF4 are discussed.
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spelling doaj-art-d357cb474c994a7eae5f060a45519b8e2025-08-20T01:48:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15848731584873The role of KLF4 in phagocyte activation during infectious diseasesToni Herta0Toni Herta1Aritra Bhattacharyya2Stefan Hippenstiel3Janine Zahlten4Department of Hepatology and Gastroenterology, Charité – Universitätsmedizin Berlin, Berlin, GermanyBerlin Institute of Health at Charité –Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Clinician Scientist Program, Berlin, GermanyDepartment of Respiratory Medicine and Critical Care Medicine with Sleep Medicine, Charité - Universitätsmedizin Berlin, Berlin, GermanyDepartment of Respiratory Medicine and Critical Care Medicine with Sleep Medicine, Charité - Universitätsmedizin Berlin, Berlin, GermanyDepartment of Respiratory Medicine and Critical Care Medicine with Sleep Medicine, Charité - Universitätsmedizin Berlin, Berlin, GermanyPhagocytes, including granulocytes (especially neutrophils), monocytes, macrophages, and dendritic cells, are essential components of the innate immune system, bridging innate and adaptive immunity. Their activation and function are tightly regulated by transcription factors that coordinate immune responses. Among these, Krüppel-like factor 4 (KLF4) has gained attention as a regulator of phagocyte differentiation, polarization, and inflammatory modulation. However, its role is highly context-dependent, exhibiting both pro- and anti-inflammatory properties based on environmental signals, cellular states, and the invading pathogen. KLF4 influences monocyte-to-macrophage differentiation and shapes macrophage polarization, promoting either inflammatory or regulatory phenotypes depending on external cues. In neutrophils, it affects reactive oxygen species production and immune activation, while in dendritic cells, it regulates monocyte-to-dendritic cell differentiation and cytokine secretion. Its diverse involvements in immune responses suggests that it contributes to maintaining a balance between effective pathogen defense and the prevention of excessive and potentially harmful inflammation. This review summarizes current knowledge on the function of KLF4 in phagocytes during infections, highlighting its regulatory mechanisms, context-dependent roles, and its impact on immune activation and resolution. Additionally, potential implications for therapeutic interventions targeting KLF4 are discussed.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1584873/fullKLF4phagocytesmacrophagesneutrophilsdendritic cellsinnate immunity
spellingShingle Toni Herta
Toni Herta
Aritra Bhattacharyya
Stefan Hippenstiel
Janine Zahlten
The role of KLF4 in phagocyte activation during infectious diseases
Frontiers in Immunology
KLF4
phagocytes
macrophages
neutrophils
dendritic cells
innate immunity
title The role of KLF4 in phagocyte activation during infectious diseases
title_full The role of KLF4 in phagocyte activation during infectious diseases
title_fullStr The role of KLF4 in phagocyte activation during infectious diseases
title_full_unstemmed The role of KLF4 in phagocyte activation during infectious diseases
title_short The role of KLF4 in phagocyte activation during infectious diseases
title_sort role of klf4 in phagocyte activation during infectious diseases
topic KLF4
phagocytes
macrophages
neutrophils
dendritic cells
innate immunity
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1584873/full
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