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. 2021 May 7;9:675099. doi: 10.3389/fcell.2021.675099

FIGURE 2.

FIGURE 2

Static gene regulatory networks of CD4 + T cell differentiation: Th17 and Tregs. Each CD4 + T cell subset can be defined by their distinct abilities to sense, program and function in the control of specific pathogen or immune pathologies. The inductive cytokines, polarizing transcription factors and cytokines or chemokine receptors that are characteristic of each subset are shown. (A) Th17 cell differentiation. The Th17 subset is a key mediator of the inflammatory response; its functional attributes are the recruitment of neutrophils that are necessary for the clearance of extracellular bacterial and fungal infections. (B) Regulatory T cell differentiation. Tregs are vital to maintaining balance in the system since they allow tolerance and prevent autoimmune diseases by suppressing the function of Effector T cells. Membrane components: TGF-β, transforming growth factor beta; TGFβR, TGF-beta receptor; IL-1β, interleukin 1-beta; IL-1βR, interleukin 1-beta receptor; MHC II, major histocompatibility complex class II; TCR, T-cell receptor; TL1A, TNF-like ligand A1; DR3, death receptor 3; CD40, cluster of differentiation 40; CD40L, CD40 ligand; ICOS, inducible T-cell co-stimulator; GITR, glucocorticoid-induced TNFR family related gene; PD1, programed cell death protein 1; OX40, tumor necrosis factor receptor superfamily, member 4; LAG3, lymphocyte-activation gene 3; 4-1BB (or CD137). BTLA, B- and T-lymphocyte attenuator; TIGIT, T cell immunoreceptor with Ig and ITIM domains; Gal-9, galectin 9; TIM3, T-cell immunoglobulin and mucin-domain containing-3; CTLA4, cytotoxic T-lymphocyte-associated protein 4. Nuclear components: SMAD, smad family members; STAT3, signal transducer and activator of transcription 3; RUNX1, runt-related transcription factor 1; BATF, basic leucine zipper ATF-like transcription factor; AHR, aryl hydrocarbon receptor; IRF4, interferon regulatory factor 4; NF-kβ, nuclear factor-kappa B; NFAT, nuclear factor of activated T-cells; AP-1, activator protein 1; PI3K, phosphoinositide 3-kinases; RORγt, RAR-related orphan receptor gamma; CREB, C-AMP response element-binding protein; FOXP3, forkhead box P3. Extracellular secretion: IL-17A, IL-17F, IL-21, IL-23, IL-22, IL-10, IL-35, and TGF-β. Black lines means a positive direct interaction. Red lines are negative direct interactions and green lines indicate a bibliographic support on the synergistic function of the components in the differentiation of cellular subtypes.