Distinct role of FoxO1 in M-CSF- and GM-CSF-differentiated macrophages contributes LPS-mediated IL-10: implication in hyperglycemia

Chung, Sangwoon; Ranjan, Ravi; Lee, Yong Gyu; Park, Gye Young; Karpurapu, Manjula; Deng, Jing; Xiao, Lei; Kim, Ji Young; Unterman, Terry G.; Christman, John W.

doi:10.1189/jlb.3a0514-251r

Cited by 74 publications

(84 citation statements)

References 76 publications

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“…We found that BMs were partially polarized to M2 based on flow cytometry and PCR, suggesting that M-CSF polarized macrophages generate an increased number of anti-inflammatory factors. Granulocyte-macrophage (GM)-CSF induces macrophages to produce higher amounts of inflammatory factors (Chung et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Comparison of the characteristics of macrophages derived from murine spleen, peritoneal cavity, and bone marrow

Zhao

Tian

Han

et al. 2017

J. Zhejiang Univ. Sci. B

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Abstract:Macrophages have a diverse set of functions based upon their activation states. The activation states, including resting (M0) and polarizing (M1 and M2) states, of macrophages derived from the mouse bone marrow, spleen, and peritoneal cavity (BMs, SPMs, and PCMs, respectively) were compared. We evaluated the macrophage yield per mouse and compared the surface markers major histocompatibility complex (MHC) II and CD86 by flow cytometry. The relative mRNA levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, mannose receptor (MR), and Ym1 in the M0, M1, and M2 states were also compared using real-time polymerase chain reaction (PCR) analysis. Bone marrow yielded the most macrophages with the best homogeneity, but they were polarized toward the M2 phenotype. All three types of macrophages had the capacity to polarize into the M1 and M2 states, but SPMs had a stronger capacity to polarize into M1. The three types of macrophages showed no differences in their capacity to polarize into the M2 state. Therefore, the three types of macrophages have distinct characteristics regardless of their resting or polarizing states. Although bone marrow can get large amounts of homogeneous macrophages, the macrophages cannot replace tissue-derived macrophages.

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Section: Discussionmentioning

confidence: 99%

Comparison of the characteristics of macrophages derived from murine spleen, peritoneal cavity, and bone marrow

Zhao

Tian

Han

et al. 2017

J. Zhejiang Univ. Sci. B

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“…In fact, these GM-CSF grown macrophages could produce even more extensive proinflammatory cytokines compared to M-CSF grown, INFγ/LPS polarized macrophages (preliminary data). Despite the remarkable inflammatory phenotype of GM-CSF grown macrophages, there is much confusion about the use of these cells because they have been used as both macrophages and DCs without any guiding criteria (Bhattacharya et al, 2011; Chung et al, 2015; Ganesh et al, 2009). Consequently, we sought to distinguish amongst the heterogenous populations of GM-CSF derived cells and especially focused on characteristics of GM-BMMs compared to GM-BMDCs in this study.…”

Section: Discussionmentioning

confidence: 99%

GM-CSF Grown Bone Marrow Derived Cells Are Composed of Phenotypically Different Dendritic Cells and Macrophages

Jung

et al. 2016

Mol Cells

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Granulocyte-macrophage colony stimulating factor (GM-CSF) has a role in inducing emergency hematopoiesis upon exposure to inflammatory stimuli. Although GM-CSF generated murine bone marrow derived cells have been widely used as macrophages or dendritic cells in research, the exact characteristics of each cell population have not yet been defined. Here we discriminated GM-CSF grown bone marrow derived macrophages (GM-BMMs) from dendritic cells (GM-BMDCs) in several criteria. After C57BL/6J mice bone marrow cell culture for 7 days with GM-CSF supplementation, two main populations were observed in the attached cells based on MHCII and F4/80 marker expressions. GM-BMMs had MHCIIlowF4/80high as well as CD11c+CD11bhighCD80−CD64+MerTK+ phenotypes. In contrast, GM-BMDCs had MHCIIhighF4/80low and CD11chighCD8α− CD11b+CD80+CD64−MerTKlow phenotypes. Interestingly, the GM-BMM population increased but GM-BMDCs decreased in a GM-CSF dose-dependent manner. Functionally, GM-BMMs showed extremely high phagocytic abilities and produced higher IL-10 upon LPS stimulation. GM-BMDCs, however, could not phagocytose as well, but were efficient at producing TNFα, IL-1β, IL-12p70 and IL-6 as well as inducing T cell proliferation. Finally, whole transcriptome analysis revealed that GM-BMMs and GM-BMDCs are overlap with in vivo resident macrophages and dendritic cells, respectively. Taken together, our study shows the heterogeneicity of GM-CSF derived cell populations, and specifically characterizes GM-CSF derived macrophages compared to dendritic cells.

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“…In monocytes for example, GM-CSF regulates the expression of TLR2 and has been shown to induce the expression of IL-12, TNF-α, and monocyte chemoattractant protein-1 (MCP-1) by JAK2/STAT5 signaling (82, 83). Similarly, in vitro treatment of macrophage lineage cells with GM-CSF shifts the polarization to an inflammatory M1 phenotype (Fig 1) that enables them to respond strongly to stimuli (84, 85). In contrast, when M-CSF is used as the sole stimulus, it shifts monocytes into an immunosuppressive M2 phenotype (86, 87).…”

Section: Introductionmentioning

confidence: 93%

GM-CSF: An immune modulatory cytokine that can suppress autoimmunity

et al. 2015

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GM-CSF was originally identified as a colony stimulating factor (CSF) because of its ability to induce granulocyte and macrophage populations from precursor cells. Multiple studies have demonstrated that GM-CSF is also an immune-modulatory cytokine, capable of affecting not only the phenotype of myeloid lineage cells, but also T-cell activation through various myeloid intermediaries. This property has been implicated in the sustenance of several autoimmune diseases like arthritis and multiple sclerosis. In contrast, several studies using animal models have shown that GM-CSF is also capable of suppressing many autoimmune diseases like Crohn's disease, Type-1 diabetes, Myasthenia gravis and experimental autoimmune thyroiditis. Knockout mouse studies have suggested that the role of GM-CSF in maintaining granulocyte and macrophage populations in the physiological steady state is largely redundant. Instead, its immune-modulatory role plays a significant role in the development or resolution of autoimmune diseases. This is mediated either through the differentiation of precursor cells into specialized non-steady state granulocytes, macrophages and dendritic cells, or through the modulation of the phenotype of mature myeloid cells. Thus, outside of myelopoiesis, GM-CSF has a profound role in regulating the immune response and maintaining immunological tolerance.

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Distinct role of FoxO1 in M-CSF- and GM-CSF-differentiated macrophages contributes LPS-mediated IL-10: implication in hyperglycemia

Cited by 74 publications

References 76 publications

Comparison of the characteristics of macrophages derived from murine spleen, peritoneal cavity, and bone marrow

Comparison of the characteristics of macrophages derived from murine spleen, peritoneal cavity, and bone marrow

GM-CSF Grown Bone Marrow Derived Cells Are Composed of Phenotypically Different Dendritic Cells and Macrophages

GM-CSF: An immune modulatory cytokine that can suppress autoimmunity

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