CSF2/GM-CSF: A Key Molecule in Immune Regulation and Disease Treatment

1. Overview of CSF2

CSF2, also known as Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), is a cytokine secreted by various cells, including T cells, B cells, macrophages, and fibroblasts ^[3]. CSF2 primarily exerts its effects by binding to receptors on target cells, thereby regulating cell proliferation, differentiation, and function. The CSF2 receptor consists of α and β chains, with the β chain playing a vital role in signal transduction ^[4]. In the immune system, CSF2 is indispensable for regulating the generation and activity of granulocytes and macrophages.

2. Structure and Function of CSF2

The molecular structure of CSF2 encompasses multiple functional domains. The N-terminal domain is responsible for binding to the α chain of the receptor, while the C-terminal domain participates in signal transduction ^[5]. Upon binding to the receptor, CSF2 activates the JAK-STAT signaling pathway, leading to the regulation of downstream gene expression ^[6]. Moreover, CSF2 can influence cell proliferation and differentiation through the PI3K-Akt and MAPK signaling pathways ^[7]. Within the immune system, CSF2 promotes the activation of macrophages, enhancing their phagocytic and bactericidal capabilities ^[8]. Additionally, CSF2 regulates the differentiation and function of T cells, maintaining the balance of immune responses ^[9].

3. Mechanisms of Action of CSF2

3.1 Inflammatory Response

During inflammatory responses, CSF2 promotes the recruitment and activation of inflammatory cells, thereby exacerbating inflammation ^[10]. Specifically, CSF2 binds to its receptor and activates the JAK-STAT signaling pathway, inducing the release of inflammatory cytokines such as IL-6 and TNF-α ^[11]. These cytokines further activate and proliferate inflammatory cells, creating a positive feedback loop that intensifies the inflammatory response. Moreover, CSF2 can promote the survival and proliferation of inflammatory cells through the PI3K-Akt signaling pathway ^[12].

3.2 Tumor Microenvironment

In the tumor microenvironment, CSF2 influences tumor progression by affecting the polarization of tumor-associated macrophages (TAMs) ^[13]. CSF2 induces the polarization of TAMs towards the M2 phenotype, enhancing their immune-suppressive functions ^[14]. M2 macrophages secrete anti-inflammatory cytokines such as IL-10 and TGF-β, which inhibit the activation and proliferation of T cells, thereby facilitating immune evasion by tumor cells ^[15]. Additionally, CSF2 can impact tumor cell proliferation and migration through the MAPK signaling pathway ^[16].

3.3 Tissue Repair and Regeneration

During tissue repair and regeneration, CSF2 promotes the activation of macrophages, enhancing their ability to clear necrotic tissue and promote tissue repair ^[17]. CSF2 activates the JAK-STAT signaling pathway, prompting macrophages to secrete growth factors such as VEGF and HGF, which promote angiogenesis and tissue repair ^[18]. Furthermore, CSF2 can enhance the survival and function of macrophages through the PI3K-Akt signaling pathway, strengthening their role in tissue repair ^[19].

4. Related Signaling Pathways

CSF2 primarily functions through the JAK-STAT signaling pathway. When CSF2 binds to its receptor, JAK2 is activated, leading to the phosphorylation of STAT5, which then dimerizes and translocates to the nucleus to regulate the expression of downstream genes ^[20]. Specifically, CSF2 promotes the release of inflammatory cytokines and the activation of inflammatory cells through the JAK2-STAT5 signaling pathway ^[21]. Additionally, CSF2 can promote cell survival and proliferation through the PI3K-Akt signaling pathway ^[22]. In certain cell types, CSF2 can also activate the MAPK signaling pathway, influencing cell differentiation and function. The activation of these signaling pathways is crucial for the role of CSF2 in immune regulation, inflammatory responses, and tumor progression.

5. Related Diseases

5.1 Inflammatory Diseases

In inflammatory diseases, CSF2 promotes the recruitment and activation of inflammatory cells, enhancing the inflammatory response ^[23]. For instance, in rheumatoid arthritis, CSF2 stimulates the activation and proliferation of inflammatory cells, exacerbating joint inflammation and destruction ^[24]. In inflammatory bowel disease, CSF2 further intensifies intestinal inflammation by promoting the activation of inflammatory cells ^[25].

5.2 Tumor Progression

In tumor development, CSF2 influences tumor growth and metastasis by promoting the polarization of tumor-associated macrophages ^[26]. For example, in gastric cancer, CSF2 enhances tumor invasion and metastasis by promoting the reprogramming of MSCs ^[1]. In breast cancer, CSF2 aids tumor cells in immune evasion and promotes tumor progression by inducing the polarization of macrophages ^[27].

5.3 Autoimmune Diseases

In autoimmune diseases, CSF2 regulates the function of immune cells, thereby impacting disease progression ^[28]. For instance, in systemic lupus erythematosus, CSF2 promotes the activation of immune cells, exacerbating the autoimmune response ^[29]. In multiple sclerosis, CSF2 influences disease progression by modulating the function of immune cells ^[30].

5.4 Infectious Diseases

In infectious diseases, CSF2 enhances the function of immune cells, improving the body's ability to combat infections ^[31]. In tuberculosis, CSF2 promotes the activation of macrophages, enhancing their bactericidal capabilities ^[32]. During viral infections, CSF2 boosts the body's antiviral response by stimulating the activation of immune cells ^[33].

6. Drug Development Progress

Currently, drug development targeting CSF2/GM-CSF primarily focuses on two areas: utilizing the immune-regulating functions of GM-CSF and its ability to stimulate bone marrow production of white blood cells to treat cancers and other diseases; and developing inhibitors of GM-CSF to reduce its levels in inflammatory and autoimmune diseases.

Several GM-CSF-based drug development pipelines are currently in progress, covering a range of cancers such as lymphoma, leukemia, and nasopharyngeal tumors, and are also considered potential targets for the treatment of autoimmune diseases. Some of the ongoing pipelines are organized in the following table:

7. Recommended Products for CSF2 Research

As an important cytokine, CSF2 plays a key role in immune regulation, inflammatory responses, and tumor progression. In-depth research on the mechanisms of CSF2 and related signaling pathways can provide new targets and strategies for the treatment of various diseases. CUSABIO has launched a range of high-activity CSF2 protein products and offers CSF2 antibodies and ELISA kits to assist your research on the mechanisms of CSF2 or its potential clinical value.

● CSF2 / GM-CSF Recombinant Proteins

Recombinant Human Granulocyte-macrophage colony-stimulating factor (CSF2)

CSB-MP006045HU

Recombinant Human Granulocyte-macrophage colony-stimulating factor (CSF2)

CSB-YP006045HU

● CSF2 / GM-CSF Antibodies

CSF2 Antibody

CSB-PA06475A0Rb

Applications: ELISA, IHC

CSF2 Antibody

CSB-PA268599

Applications: ELISA, WB, IHC

● CSF2 / GM-CSF ELISA Kits

Human GM-CSF ELISA Kit

CSB-E04568h

Mouse GM-CSF ELISA Kit

CSB-E04569m

Rat G-CSF ELISA Kit

CSB-E07340r