Transcriptional regulation of CD4 + T H cells that mediate tissue inflammation

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Tiffany T. Loo¹  Yuanyuan Gao¹  Vanja Lazarevic¹ 

[1] Experimental Immunology Branch, National Cancer Institute, National Institutes of Health

关键词: CD4+ T helper cells;    transcription factors;    functional plasticity;    pathogenic T cells;   

DOI  :  10.1002/JLB.1RI0418-152RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Acquired and genetic immunodeficiencies have revealed an indispensable role for CD4+ T cells in the induction of protective host immune responses against a myriad of microbial pathogens. Influenced by the cytokines present in the microenvironment, activated CD4+ T cells may differentiate into several highly-specialized helper subsets defined by the production of distinct signature cytokines tailored to combat diverse classes of pathogens. The process of specification and differentiation is controlled by networks of core, master, and accessory transcription factors, which ensure that CD4+ T helper (TH) cell responses mounted against an invading microbe are of the correct specificity and type. However, aberrant activation or inactivation of transcription factors can result in sustained and elevated expression of immune-related genes, leading to chronic activation of CD4+ TH cells and organ-specific autoimmunity. In this review, we provide an overview of the molecular basis of CD4+ TH cell differentiation and examine how combinatorial expression of transcription factors, which promotes genetic plasticity of CD4+ TH cells, can contribute to immunological dysfunction of CD4+ TH responses. We also discuss recent studies which highlight the potential of exploiting the genetic plasticity of CD4+ TH cells in the treatment of autoimmune and other immune-mediated disorders.

【 授权许可】

CC BY