STATs signaling pathways in dendritic cells: As potential therapeutic targets?

Abstract

Dendritic cells (DCs) are professional antigen-presenting cells (APCs), including heterogenous populations with phenotypic and functional diversity that coordinate bridging innate and adaptive immunity. Signal transducer and activator of transcriptions (STAT) factors as key proteins in cytokine signaling were shown to play distinct roles in the maturation and antigen presentation of DCs and play a pivotal role in modulating immune responses mediated by DCs such as differentiation of T cells to T helper (Th) 1, Th2 or regulatory T (Treg) cells. This review sheds light on the importance of STAT transcription factors’ signaling pathways in different subtypes of DCs and highlights their targeting potential usages for improving DC-based immunotherapies for patients who suffer from cancer or diverse autoimmune conditions according to the type of the STAT transcription factor and its specific activating or inhibitory agent.

GraphicAL Abstract

PLAIN LANGUAGE SUMMARY

What is the context?

Multiple disorders, including different infectious and autoimmune diseases and cancers, have affected many individuals all around the world. One of the main methods for combating such diseases is immunotherapy based on the dendritic cell (DC) vaccine. DCs are the most potent antigen-presenting cells for developing T lymphocytes’ potential to eliminate external and internal harmful factors. Manipulating DCs’ different signaling pathways, such as activating or blocking inhibitory or activatory pathways, based on our purpose is a great method for achieving efficient DC vaccines. The signal transducer and activator of transcription (STAT) is a protein with six subtypes that exists in DCs and conducts specific signaling pathways. Changing the activity of each STAT via various methods and drugs can affect DCs differently. Furthermore, each DC-existing STAT can play a specific role in establishing a special kind of disease. Thus, STAT proteins and their related signaling pathways have attracted many scientists’ attention.

What does the review highlight?

We provide a comprehensive overview of different STATs’ roles in DC subsets. Moreover, we conducted this review to identify if DC-associated STATs have any role in starting a special kind of disease. The effects of different drugs on STATs in DCs were also investigated.

What is the impact?

Generalabsly, STAT1, STAT2, and STAT4 with activatory roles, STAT3 with inhibitory roles, and STAT5 and STAT6 with both inhibitory and activatory roles can affect DCs in different conditions. Targeting different STATs in DCs with specific drugs contributes to alleviating various disease symptoms.

Keywords:

• Autoimmune disease
• cancer
• dendritic cell
• JAK/STAT signaling
• T cell

Acknowledgement

Figures were created using the BioRender online tool.

Disclosure statement

The authors declare that there is no conflict of interest.

Author contributions

Behzad Baradaran: the corresponding author of the manuscript, supervised, revised, and commented on the manuscript. Sepideh Sohrabi, Bahar Naseri, Farid Ghorbaninezhad, Shiva Alipour, Tohid Kazemi, Javad Ahmadian Heris, Leili Aghebati Maleki, Pedram Basirjafar, Raziyeh Zandvakili and Mohammad Amin Doustvandi: collected the data and wrote the primary version of the manuscript. Javad Masoumi: contributed to the design of the study and edited the manuscript.

Additional information

Funding

This study was supported by the Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.