BRIEF RESEARCH REPORT article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
A data-driven model of macrophage polarization states reveals an IFN macrophage signature in active Crohn's disease
Provisionally accepted
- 1University of California Los Angeles Department of Microbiology Immunology & Molecular Genetics, Los Angeles, United States
- 2University of California Los Angeles Division of Digestive Diseases, Los Angeles, United States
- 3University of California Los Angeles Department of Medicine, Los Angeles, United States
- 4Institute for Quantitative and Computational Biosciences, Los Angeles, United States
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Macrophages are key innate immune cells responsible for initiating and coordinating immune responses. A major determinant of macrophage function is their tissue-context-dependent polarization state, regulated by the cytokines present in the tissue microenvironment. Yet, the capability of characterizing macrophage polarization states in clinical studies remains limited. Here, we used a defined set of cytokines to polarize human PBMC derived macrophages and determine their transcriptional signatures and stimulus responsiveness. The resultant atlas of transcriptional signatures for human macrophage polarization states was applied to a dataset of intestinal biopsies from Crohn's disease patients and healthy controls. Our analysis identified a dominant population of IFNγ-polarized macrophages in areas of active Crohn's intestinal inflammation and a loss of wound healing IL-4-, IL-10-and IL-13-polarized macrophages. This study demonstrates that in vitro datasets of macrophages in defined conditions can be leveraged to interpret the functionality of cells transcriptional profiled in clinical studies.
Keywords: Macrophage polarization, Crohn's disease, Inflammatory bowel disease, scRNAseq, Macrophages, mucosal immunology
Received: 17 Sep 2025; Accepted: 18 Nov 2025.
Copyright: © 2025 Lowe, Leitman, Yan and Hoffmann. 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:
Sarina C Lowe, sclowe@mednet.ucla.edu
Alexander Hoffmann, ahoffmann@g.ucla.edu
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