Figure 3.

Regulatory programs for plasticity and functional polarization in helper lymphocytes. (a) Scheme for functional polarization within adaptive, innate, and innate-like helper lymphocytes. Upon activation, naive and progenitor lymphocytes (Th0, ILCp, or NKTp) will proceed along a polarization pathway based upon the type of infection and microenvironmental cues. Type 1, 2, and 3 immune cells are polarized in response to intracellular bacteria or viruses, helminths, and extracellular bacteria or fungi, respectively. Based upon danger signals and pathogen-associated molecular patterns, antigen-presenting cells release soluble cytokines (on top of cells) that activate JAK/STAT signaling through the relevant cytokine receptors. This is followed by activation of an LDTF by STAT, as shown, which drives initial stages of polarization. Signature TFs and cytokines for the three functional phenotypes are shown. (b) ILC3 plasticity. Indicated are cell types, transcription factors (inside cells), and soluble cytokines (outside cells) thought to be important for stepwise conversion of ILC3s to ILC1s. External signals that drive conversion events are indicated above the arrows. Abbreviations: ILC1, group 1 innate lymphoid cell; ILCp, ILC progenitor; LDTF, lineage-determining transcription factor; NKT, natural killer T; NKTp, NKT progenitor; Th, T helper; Th0, naive Th.