Dataset Information

Effects of IL-34 on Macrophage Immunological Profile in Response to Alzheimer's-Related A?42 Assemblies.

ABSTRACT: Interleukin-34 (IL-34) is a recently discovered cytokine that acts as a second ligand of the colony stimulating factor 1 receptor (CSF1R) in addition to macrophage colony-stimulating factor (M-CSF). Similar to M-CSF, IL-34 also stimulates bone marrow (BM)-derived monocyte survival and differentiation into macrophages. Growing evidence suggests that peripheral BM-derived monocyte/macrophages (BMMO) play a key role in the physiological clearance of cerebral amyloid ?-protein (A?). A?42 forms are especially neurotoxic and highly associated with Alzheimer's disease (AD). As a ligand of CSF1R, IL-34 may be relevant to innate immune responses in AD. To investigate how IL-34 affects macrophage phenotype in response to structurally defined and stabilized A?42 oligomers and preformed fibrils, we characterized murine BMMO cultured in media containing M-CSF, IL-34, or regimens involving both cytokines. We found that the immunological profile and activation phenotype of IL-34-stimulated BMMO differed significantly from those cultured with M-CSF alone. Specifically, macrophage uptake of fibrillar or oligomeric A?42 was markedly reduced following exposure to IL-34 compared to M-CSF. Surface expression of type B scavenger receptor CD36, known to facilitate A? recognition and uptake, was modified following treatment with IL-34. Similarly, IL-34 macrophages expressed lower levels of proteins involved in both A? uptake (triggering receptor expressed on myeloid cells 2, TREM2) as well as A?-degradation (matrix metallopeptidase 9, MMP-9). Interestingly, intracellular compartmentalization of A? visualized by staining of early endosome antigen 1 (EEA1) was not affected by IL-34. Macrophage characteristics associated with an anti-inflammatory and pro-wound healing phenotype, including processes length and morphology, were also quantified, and macrophages stimulated with IL-34 alone displayed less process elongation in response to A?42 compared to those cultured with M-CSF. Further, monocytes treated with IL-34 alone yielded fewer mature macrophages than those treated with M-CSF alone or in combination with IL-34. Our data indicate that IL-34 impairs monocyte differentiation into macrophages and reduces their ability to uptake pathological forms of A?. Given the critical role of macrophage-mediated A? clearance in both murine models and patients with AD, future work should investigate the therapeutic potential of modulating IL-34 in vivo to increase macrophage-mediated A? clearance and prevent disease development.

SUBMITTER: Zuroff LR

PROVIDER: S-EPMC7378440 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Effects of IL-34 on Macrophage Immunological Profile in Response to Alzheimer's-Related Aβ<sub>42</sub> Assemblies.

Zuroff Leah R LR Torbati Tania T Hart Nadav J NJ Fuchs Dieu-Trang DT Sheyn Julia J Rentsendorj Altan A Koronyo Yosef Y Hayden Eric Y EY Teplow David B DB Black Keith L KL Koronyo-Hamaoui Maya M

Frontiers in immunology 20200716

Interleukin-34 (IL-34) is a recently discovered cytokine that acts as a second ligand of the colony stimulating factor 1 receptor (CSF1R) in addition to macrophage colony-stimulating factor (M-CSF). Similar to M-CSF, IL-34 also stimulates bone marrow (BM)-derived monocyte survival and differentiation into macrophages. Growing evidence suggests that peripheral BM-derived monocyte/macrophages (BMMO) play a key role in the physiological clearance of cerebral amyloid β-protein (Aβ). Aβ<sub>42</sub> ...[more]

PMID: 32765504

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Dataset Information

Effects of IL-34 on Macrophage Immunological Profile in Response to Alzheimer's-Related A?42 Assemblies.

Publications

Effects of IL-34 on Macrophage Immunological Profile in Response to Alzheimer's-Related Aβ<sub>42</sub> Assemblies.

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