Role of c-Maf and its regulatory networks开题报告

1. 研究目的与意义（文献综述包含参考文献）

In terms of research, there have been a few studies conducted in this area in the past. Researchers aim to show how understanding c-Mafs role in macrophage polarization and its role in immune regulation can contribute in improving treatment of immunological disorders and diseases. Liu et al, showed how c-Maf regulates M2-like macrophage polarization through various methodology and proved expression of c-Maf in M2-like macrophages and its importance in regulating M2-like macrophage mediated T cell immunosuppression, also showed genes directly regulated by c-Maf in M2-like macrophages (CSF-1R) and how it influences immunosuppressive functions via gene regulation, in addition they showed how M2-like macrophage polarization and activation can be prompted through the regulation of M2-like macrophage metabolic pathways by c-Maf.Macrophages infiltrating tumors can acquire distinct phenotypes and functions resulting in the depletion of anti-tumor activity and introduction of tumor-supporting functions, and have been labeled as tumorassociated macrophages (TAMs) with M2-like features displaying their utmost plasticity within healthy tissues [12]. Because TAMs have been shown to be leaning towards the M2-like phenotype especially in the late stages of tumor progression, c-Maf was found to be highly expressed in TAMs. c-Maf has also been shown to regulate Tumor associated macrophages (TAMs), being highly expressed in TAMs c-Maf boosts TAMs immunosuppressive function, controls their metabolic programming and stimulates the production of macrophage differentiation protein CSF1R [1]. Here we note that targeting of c-Maf can inhibit production of CSF1R in return halting the polarization of TAMs to immunosuppressive M2 macrophages stipulating that c-Maf can be novel target for immunotherapy.In macrophages, c-Maf is the transcription factor that is required for the expression of the IL-10 gene. Cao S et al demonstrated this point through a series of experiments coming to a conclusion that the transcription factor c-Maf is required for the generation of IL-10 in inflammatory macrophages [3]. Emphasizing that c-Maf is vital in macrophage activity and it explicates its transcriptional mechanism in IL-10 gene regulation. Pfnder P et al, conducted their research on Cdk5 interaction with c-Maf and Il-10 in macrophages and showed that in the course of inflammation, deletion of Cdk5 causes macrophages to produce c-Maf and hence Il-10 resulting in an increased anti-inflammatory response [4].The transcription factor c-Maf governs perivascular macrophage phenotypes in a variety of tissues, including white adipose tissue where its absence from mouse vasculature-associated macrophages results in enhanced vascularization and metabolic syndrome protection [6]. c-Maf is also very important in the contribution of the initiation and transcriptional programming of perivascular macrophages across tissue as shown by Silva et al.Role of c-Maf in immune regulation through macrophage polarization has been shown by previous researchers. Liu et al showed that c-Maf deletion in myeloid cells lowers tumor development and immunosuppression while increasing antitumor development and immunosuppression while increasing antitumor T cell Immunity thus making-Maf a critical molecular gatekeeper that regulates macrophage polarization in turn governing immune suppression in cancer. And they also showed that using natural compounds such as β-glucan to target immunosuppressive macrophages through c-Maf suppression could be a unique way to improve to improve current cancer immunotherapies for instance immunocheckpoint inhibitor therapy.Although this topic has been researched before I think it still has potential to contribute in immune regulation and discovery of novel targets to be explored in immunotherapies

2. 研究的基本内容、问题解决措施及方案

The aim of this research is to answer the question Is c-Maf essential for immune regulation through macrophage polarization? Therefore what needs to be done is research on how c-Maf regulates macrophage polarization and how this applies to immune regulation. The methodology I expected to use was researching previous scholarly articles related to my topic and then performs laboratory studies on molecular mechanisms by which c-Maf regulates macrophages polarization with collaboration from fellow students and advisor. The laboratory work will require special equipment such as assay equipment and also samples of chemicals and small animals such as mice. For the acquiring of animals for testing we are supposed to go through proper channels to get permits for testing in order to avoid ethical violations and restrictions. The problem with this is not being to access the laboratory due to pandemic lockdown restrictions, therefore until now we have not done any lab work or collaborate with other students to do the project. The only thing I have been able to accomplish is studying of past literature papers in relation to my topic. I have acquired a lot of previousknowledge but will not be able to have laboratory research work to back up my theories. Researchers have shown the regulation of immunosuppressive action of macrophages by c-Maf. Since there are no many academic research papers in relation to my topic, from my research I expect to be able to show how c-Maf contributes to macrophage polarization and transcriptional regulation and how it affects immune regulation. This study is particularly significant because, from the results I was hoping to be able to devise if c-Mafs contribution to immune regulation can open up possibilities for novel therapy targets during immunotherapies. And since targeted therapy is often highly effect this could improve the efficiency of immunotherapies.Structure of the research The study will comprise of five sections; Abstract, introduction, literature review, methodology and findings and finally references. The abstract highlights research topic, the research problem, aims and objectives of the study, rationale and significance. It gives a quick overview of the research. The introduction includes background and brief introduction of our topic.In the literature review we determine the study variables as well as many theories and backgrounds pertaining to the views and opinions of various researchers. It entails the creation of a theoretical framework as well as the formulation of hypothesis.The methodologies and strategies utilized in a research study to assess the results are identified in methodology, and it covers data collection methods and strategies as well as ethical issues and restrictions. In findings numerous strategies and procedures are used to analyze and evaluate data acquired from various sources. An analysis of the results and discussion take up a major chunk of this section.The conclusion and references are the studys final section. It summarizes the studys findings and brings the whole thing to a close.