How does the dose-dependent GM-CSF differentiate multipotent progenitor cells?
The proliferation of macrophage progenitors is stimulated by GM-CSF at the lowest levels, followed by granulocyte, erythroid, eosinophil, megakaryocyte, and multipotent progenitor cells, depending on the concentration. In some cases, it also regulates eosinophil function and encourages myeloid leukemia cells to differentiate. ^[3]
 
What is the importance of GM-CSF in clinical and research use?
There are two groups of innate immune cells, dendritic cells (DC) and macrophages (Mφ), playing a crucial function in an inflammatory environment as a bridge between the innate and adaptive immune responses. ^[4] Coincidentally, GM-CSF involves in the development of both cells before they have abilities to actual against infectious substances or tumor cells.

♦ DCs development and differentiation
DC is the immune system's most effective professional antigen-presenting cell. Because of the lack of inflammation and high GM-CSF concentrations in the local environment, immature DC very seldom travels into peripheral tissues to differentiate into mature DC under steady-state circumstances. They serve as the immune system's sentinels in an immature form, constantly monitoring the surroundings for antigens. ^[5] After antigen uptake, exogenous and endogenous antigens are presented in MHC class II complexes and MHC class I complexes on the cell surface. Accordingly, for example, CD8⁺ T cells can be activated by DC which presents the tumor antigens. DC travels to the lymphoid organs when they are mature, where they offer the antigen to naïve T cells. After that, the activated T cells multiply and move from the lymph organs to seek out and kill cells in an antigen-dependent way.
DC vaccination was initially investigated in a clinical experiment in the 1990s to induce or enhance an efficient antitumor immune response against tumor antigens in cancer patients. In 1994, it was found that the immature DC may be generated from monocytes or some other progenitors by cultivating them in the presence of IL-4 and GM-CSF. This discovery made it possible to obtain DCs in large quantities to expedite clinical trials. ^[6,7,8]
 

♦ M1/M2 macrophages polarization
GM-CSF stimulates the activation of monocytes/macrophages as well as the differentiation of these cells into other states that participate in immune responses.
Macrophages are heterogeneous cells that can quickly alter their function in response to signals from the surrounding microenvironment. IFN-γ, GM-CSF, and other cytokines can activate classically activated M1 Mφ which plays a crucial role in antitumor immunity and safeguard the body from a variety of infectious molecules.
And alternatively activated M2 Mφ are differentiated by IL-4, M-CSF, and other cytokines. They mainly control wound healing and have anti-inflammatory properties. ^[9,10]


 

Related products: 
→ G-CSF, Human 
→ M-CSF, Human
→ SCF, Human
→ TPO, Human
→ IL-1 alpha, Human
→ IL-1 beta, Human
→ IL-2, Human
→ IL-3, Human
→ IL-4, Human
→ IL-5, Human
→ IL-6, Human
→ IL-10, Human
→ IL-13, Human
→ IL-21, Human
→ IL-33, Human
→ IFN-γ, Human
→ TNF-α, Human 
→ TGFβ-1, Human

 

 

1. Lutz MB, Kukutsch N, Ogilvie AL, Rössner S, Koch F, Romani N, Schuler G. An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J Immunol Methods. 1999 Feb 1;223(1):77-92.
2. Palle P, Monaghan KL, Milne SM, Wan ECK. Cytokine Signaling in Multiple Sclerosis and Its Therapeutic Applications. Med Sci (Basel). 2017 Oct 13;5(4):23
3. Burgess AW, Metcalf D. The nature and action of granulocyte-macrophage colony stimulating factors. Blood. 1980 Dec;56(6):947-58
4. Lotfi N, Thome R, Rezaei N, Zhang GX, Rezaei A, Rostami A, Esmaeil N. Roles of GM-CSF in the Pathogenesis of Autoimmune Diseases: An Update. Front Immunol. 2019 Jun 4;10:1265.
5. Jakubzick C, Gautier EL, Gibbings SL, Sojka DK, Schlitzer A, Johnson TE, Ivanov S, Duan Q, Bala S, Condon T, van Rooijen N, Grainger JR, Belkaid Y, Ma'ayan A, Riches DW, Yokoyama WM, Ginhoux F, Henson PM, Randolph GJ. Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. Immunity. 2013 Sep 19;39(3):599-610.
6. Bol KF, Schreibelt G, Gerritsen WR, de Vries IJ, Figdor CG. Dendritic Cell-Based Immunotherapy: State of the Art and Beyond. Clin Cancer Res. 2016 Apr 15;22(8):1897-906.
7. Sallusto F, Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med 1994;179:1109–18.
8. Lutz MB, Strobl H, Schuler G, Romani N. GM-CSF Monocyte-Derived Cells and Langerhans Cells As Part of the Dendritic Cell Family. Front Immunol. 2017 Oct 23;8:1388.
9. Fang P, Li X, Dai J, Cole L, Camacho JA, Zhang Y, Ji Y, Wang J, Yang XF, Wang H. Immune cell subset differentiation and tissue inflammation. J Hematol Oncol. 2018 Jul 31;11(1):97. doi: 10.1186/s13045-018-0637-x. PMID: 30064449; PMCID: PMC6069866.
10. Kumar A, Taghi Khani A, Sanchez Ortiz A, Swaminathan S. GM-CSF: A Double-Edged Sword in Cancer Immunotherapy. Front Immunol. 2022 Jul 5;13:901277. doi: 10.3389/fimmu.2022.901277. PMID: 35865534; PMCID: PMC9294178.