Fac Rev 2021 15;10:30. Epub 2021 Mar 15.
Molecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
For over 35 years since Mosmann and Coffman proposed the seminal "type 1 T helper (Th1)/type 2 T helper (Th2)" hypothesis in 1986, the immunological community has appreciated that naïve CD4 T cells need to make important decisions upon their activation, namely to differentiate towards a Th1, Th2, Th17 (interleukin-17-producing T helper), follicular T helper (Tfh), or regulatory T cell (Treg) fate to orchestrate a variety of adaptive immune responses. The major molecular underpinnings of the Th1/Th2 effector fate choice had been initially characterized using excellent reductionist culture systems, through which the transcription factors T-bet and GATA3 were identified as the master regulators for the differentiation of Th1 and Th2 cells, respectively. However, Th1/Th2 cell differentiation and their cellular heterogeneity are usually determined by a combinatorial expression of multiple transcription factors, particularly , where dendritic cell (DC) and innate lymphoid cell (ILC) subsets can also influence T helper lineage choices. Read More