Mutation in the rat interleukin 34 gene impacts macrophage development, homeostasis, and inflammation
Interleukin 34 (IL34) and colony-stimulating factor 1 (CSF1) signal through a shared receptor (CSF1R) to control macrophage survival, differentiation, and function. Here, we describe the impact of loss-of-function mutation in the rat <i>Il34</i> gene. In contrast to IL34 mutant mice, macrophages within squamous epithelia (Langerhans cells) were not significantly depleted in <i>Il34</i> <sup>-/-</sup> rats. In the brain, microglia and brain-associated macrophages were selectively depleted in grey matter. A gradient of microglial density in the <i>Il34</i> <sup>-/-</sup> cortex suggests that CSF1 can diffuse outwards from the corpus callosum. Microglial loss was not associated with detectable neuropathology or altered gene expression in the cortex, hippocampus, and thalamus aside from selective loss of microglia-expressed transcripts. In the adenine diet model of renal interstitial fibrosis, both <i>Il34</i> and <i>Csf1</i> were induced. The absence of IL34 led to a significant reduction in macrophage recruitment compared with controls, but pathology was unaffected. We suggest that IL34 and CSF1 provide overlapping signals to sustain microglia and to direct macrophage recruitment and repair tissue injury in the periphery.
Authors
- Ginell Ranpura
- Emma K. Green
- Nyoman D. Kurniawan (ORCID: https://orcid.org/0000-0001-6340-182X)
- Emma Maxwell
- Rachel Allavena (ORCID: https://orcid.org/0000-0001-5126-7125)
- Allison R. Pettit (ORCID: https://orcid.org/0000-0003-4707-7892)
- Sarah Schulze (ORCID: https://orcid.org/0000-0002-9140-8276)
- Damion H. R. Stimson (ORCID: https://orcid.org/0000-0002-8643-6539)
- Dylan Carter‐Cusack (ORCID: https://orcid.org/0000-0003-3190-905X)
- Gary Cowin (ORCID: https://orcid.org/0000-0002-3400-3109)
- Katharine M. Irvine (ORCID: https://orcid.org/0000-0002-6716-1605)
- Sahar Keshvari (ORCID: https://orcid.org/0000-0002-8116-8889)
- Susan Millard (ORCID: https://orcid.org/0000-0003-1738-3362)
- Stephen Huang (ORCID: https://orcid.org/0000-0002-1127-8898)
- Jeeva Kanesarajah (ORCID: https://orcid.org/0000-0001-5776-128X)
- Omkar L. Patkar (ORCID: https://orcid.org/0000-0003-1543-2060)
- David Hume (ORCID: https://orcid.org/0000-0002-2615-1478)
Institutions
- Translational Research Institute (AU)
- The University of Queensland (AU)
- QIMR Berghofer Medical Research Institute (AU)
- Mater Research (AU)
- National Imaging Facility (AU)
Publication Details
- Journal
- Life Science Alliance
- Published
- 2025-06-18
- DOI
- https://doi.org/10.26508/lsa.202503264
- Citations
- 1
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.84
Funders
- Mater Foundation
- National Imaging Facility
- National Health and Medical Research Council