Transcription Factors

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Transcription Factors and Immunity

The process of transcription initiation in eukaryotes is extremely complex requiring the assistance of multiple proteins and factors, among which transcription factors refer to a group of functional small proteins initiating and regulating the gene transcription by binding to specific DNA sequences. Transcription factors directly recognize and interpret the genome, which is the first step of performing the DNA decoding sequence. Then they turn on or off gene transcription and control the transcription rate to ensure that the cells are normally developed and functioning properly at the right time.

The immune system is subtly regulated at several levels to ensure normal responses are elicited when challenged by exogenous stimulations or self-antigens. Multiple transcription factors have been conclusively shown to be necessary and significant for the development of the immune system and various immune defenses (both adaptive and innate immunity). These transcription factors, such as Foxo3, GATA3, T-bet, NF-κB, PU.1, etc., together with related genes and pathways have been demonstrated to widely associated with a remarkably diverse range of immune process, including the commitment and differentiation of immune cell lineages; effector functions of T lymphocytes by regulating the secretion of cytokines; tailoring specific immune responses in response to different antigen stimulations; the formation of immune “memory”; and so forth. And abnormalities and mutations in transcription factors result in diverse human diseases.

Complex network of cytokines and transcription factors for generation and function of T cells. Fig.1 Complex network of cytokines and transcription factors for generation and function of T cells. (Asadi-Samani, 2017)

The Significance of Transcription Factors for γδ T Cell

γδ T cells are a small proportion of T lymphocytes with a γδ T-cell receptor (TCR), which are distinct from common T cells expressing αβ TCR. αβ T cells and γδ T cells are conserved lymphocyte lineages arising from the thymus and resident in various tissues where they coordinate to provide rapid and accurate immune defense and protections to the host.

In adult humans, γδ T cells represent a minor subset of circulating T lymphocytes (<5%) mainly distribute in epithelial mucosa tissues. Different from αβ T cells, γδ T cells mediate rapid immune responses by recognizing a broad spectrum of antigens in a major histocompatibility complex (MHC) dependent or independent manner. TCRs on the surface of γδ T cells recognize various environmental ligands or self-antigens and induce signal cascade, resulting in the expression of several critical transcription factors that drive and control γδ T cell effector functions. These transcriptional regulators are of vital importance for the differentiation, programming, and effector fates of γδ T cells. Currently, multiple transcription factors have been characterized to regulate and influence the effector functions of γδ T cells in different mechanisms (showing in the following table).

T cell differentiation significantly enhances the understanding of their development. Fig.2 γδ T cell differentiation significantly enhances the understanding of their development. (Sagar, 2018)

Table.1 several critical transcription factors for γδ T cells.

Transcription Factor Attribute Functions for γδ T Cells
T-bet T-box expressed in T cells Induce the production of IFN-γ
PU.1 An Ets family transcription factor Associate with homeostasis and may be negative for cell expansion
RORγt A nuclear receptor of transcription factors Master the expression of interleukin-17
SOX13 A member of the SOX family Essential for the development and differentiation
c-Maf The AP-1 family of basic region/leucine zipper factor Essential for commitment and maintenance of all interleukin-17-producing γδ T cells
Eomes A T-box transcription factor A marker for the differentiation


  1. Asadi-Samani, M., et al. Inhibition of Th1 and Th17 Cells by Medicinal Plants and Their Derivatives: A Systematic Review. Phytotherapy Research. 2017, 31(8): 1128-1139.
  2. Sagar, S., et al. Deciphering the Regulatory Landscape of ɣδ T Cell Development by Single-Cell RNA Sequencing. The EMBO Journal. 2018, 39(13): e104159.
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