Synergistic and combinatorial control of T cell activation and differentiation by transcription factors.
Naïve CD4(+) T cells are educated in the thymus to survey the periphery for cognate antigen while ignoring self or commensal antigens. T cell antigen receptor (TCR) cross-linking initiates signaling cascades that integrate information from co-stimulatory receptors and locally available cytokines to chart the course of inflammation. The dynamic composition of transcription factors acting within a given T cell drive clonal expansion and specify differentiation into a growing array of effector and regulatory T cell subsets. The classical gamma-interferon (IFNgamma)-secreting T helper type (Th)-1 and IL-4-producing Th2 cell subsets utilize T-bet or GATA3 as master lineage regulators. It is now understood that naïve T cells also differentiate into pro-inflammatory Th17 or tissue-protective inducible T regulatory (iTreg) cells under the respective guidance of RORgammat or FOXP3. Emerging data highlight the reoccurring theme that these Th17 and iTreg master regulators prescribe T cell lineage commitment through interactions with each other, as well as with a broader network of auxiliary transcription factors.
Sundrud
Mark S
MS
Tempero pharmaceuticals, Inc., Cambridge, MA 02139, USA. msundrud@temperopharma.com
Nolan
Michael A
MA
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D014157:Transcription Factors