Natural Killer T (NKT) Cells and Periodontitis: Potential Regulatory Role of NKT10 Cells

Figure 2

Maturation and differentiation of NKT cells. (a) According to the linear maturation model, mice NKT cells go through four maturation stages, from S0 to S3. After antigen presentation, NKT cells progress from an immature stage S0 as CD24⁺CD44^-NK1.1^- cells to stage S1 as IL-4-producing CD24^-CD44^-NK1.1^- cells, depending on the activation of transcription factors PLZF and GATA3. After activation of the transcription factor RORγt, cells mature to stage S2 as CD24^-CD44⁺NK1.1^- cells, which also produce IL-4. Finally, activation of the transcription factor T-bet promotes maturation to state S3 as CD24^-CD44⁺NK1.1^-/+ cells, which produce IFN-γ. (b) After the antigenic presentation, NKT0 EGR2⁺CD24⁺CD44^-NK1.1^- progenitor cells differentiate to CD4⁺IL17RB^- precursor cells in a manner dependent on the activation of the transcription factor PLZF. After the activation of the transcription factors T-bet, GATA3, RORγt, or E4BP4, the precursor NKT cells acquire the potential to differentiate into IFN-γ-producing NKT1 T-bet⁺CD122⁺IL17RB^-, IL-4-producing NKT2 GATA3⁺CD4⁺CD27⁺IL17RB⁺, IL-17A-producing NKT17 RORγt⁺CD4^-CD27^-IL17RB^+/-, or IL-10-producing NKT10 E4BP4⁺CD152⁺NK1.1⁺ cells. APCs, antigen-presenting cells; CD, cluster of differentiation; EGR2, early growth response protein-2; E4BP4, transcription factor E4 promoter-binding protein 4; GATA3, transcription factor GATA binding protein 3; IFN, interferon; IL, interleukin; NK1.1, Natural Killer cell pectin-like receptor subfamily B molecule member 1; NKT, Natural Killer T cell; NKTp, Natural Killer T cell precursor; NKT0, Natural Killer T cell progenitor; PLZF, promyelocytic leukemia zinc finger; RORγt, transcription factor retinoic acid-related orphan nuclear receptor γt; T-bet, transcription factor T-box; TCR, T-cell receptor. (Created with http://BioRender.com).

(a) Linear Maturation

(b) Linear Differentiation