Comprehensive overview of CD4+ T cell subsets: induction, transcription factors, post-induction cytokines, roles in host protection, and associated pathologies
| CD4+ T cell subsets | Inducing cytokines | Transcription factors | Post-induction cytokines | Roles in host protection | Associated pathologies | References |
|---|---|---|---|---|---|---|
| Th1 | IL-12, IFN-γ, IFN-α, IL-2, and IL-4 | T-bet, STAT1, and STAT4 | IFN-γ, IL-2, IFN-α, TNF-α, and TNF-γ | Defense against intracellular pathogens | Autoimmune diseases and pregnancy complications | [24, 27, 32–39] |
| Tumor progression (when decreased) | ||||||
| Th2 | IL-4, IL-2, and IL-6 | GATA3, STAT6, MAF, and NFAT | IL-13, IL-4, IL-5, IL-10, IL-6, and IL-9 | Defense against extracellular pathogens | Allergic diseases such as asthma and eczema | [24, 27, 33, 35, 36, 38–42] |
| Th17 | TGF-β, IL-6, IL-21, IL-23, and IL-1 | RORγt, STAT3, RORα, and RUNX1 | IL-17A, IL-22, IL-17F, IL-21, GM-CSF, TNF-α, IFN-γ, IL-26, IL-10, and IL-9 | Defense against intracellular and extracellular pathogens | Inflammatory bowel disease, rheumatoid arthritis, psoriasis, multiple sclerosis, and bone inflammation | [27, 35, 38, 46–52] |
| Fungal diseases (when decreased) | ||||||
| Treg | TGF-β, IL-2, and IL-35 | Foxp3, STAT5, and RUNX1/3 | IL-10, TGF-β, and IL-35 | Immune homeostasis and preventing autoimmunity | Tumor progression | [27, 35, 38, 48, 57–62] |
| Autoimmune diseases (when decreased) | ||||||
| Th9 | TGF-β, IL-4, IL-1, IL-25, IL-33, IL-2, IL-10, IL-21, TNF-α, IL-6, and IL-7 | PU.1, IRF4, STAT6, GATA3, STAT5, NFκB, STAT1, FoxO1, IRF1/8, and BATF | IL-9, IL-10, IL-5, IL-13, and IL-21 | Skin immunity | Autoimmune and inflammatory diseases including atopic dermatitis and asthma | [35, 38, 71–78] |
| Anti-tumor response | ||||||
| Protection against helminth infections | ||||||
| Th22 | IL-6, TNF-α, IL-1β, IL-21, and IL-26 | AHR, STAT3, STAT1, STAT5, RORγt, and HIF-1A | IL-22, IL-13, IL-26, TNF-α, and IL-10 | Cutaneous, intestinal, and respiratory barrier immunity | Inflammatory bowel diseases, thyroid diseases, immune thrombocytopenia, asthma, multiple sclerosis, rheumatoid arthritis, hepatitis, nephropathy, myasthenia gravis, and certain types of tumors | [35, 38, 79–86] |
| Augmentation of intrinsic immunity | ||||||
| Regeneration of tissues | ||||||
| Tfh | IL-21, IL-12, IL-6, TGF-β, IL-23, IL-27, IL-2, and IFN-γ | Bcl6, STAT1, STAT3, STAT4, STAT5, BATF, IRF4, MAF, FoxO1, and T-bet | IL-21, IL-4, IFN-γ, IL-17, IL-13, IL-10, and IL-5 | Critical role in supporting B cell maturation and differentiation into effector and memory B cells | Autoimmunity and T cell lymphoma | [35, 38, 87–94] |
| Humoral immunodeficiency (when decreased) |
IFN-γ: interferon-gamma; STAT1: signal transducer and activator of transcription 1; TNF-α: tumor necrosis factor-alpha; MAF: v-maf musculoaponeurotic fibrosarcoma oncogene homolog; NFAT: nuclear factor of activated T cell; RORγt: retinoic acid receptor-related orphan receptor gamma-t; RUNX1: runt-related transcription factor 1; GM-CSF: granulocyte-macrophage colony-stimulating factor; PU.1: Spi-1 proto-oncogene; IRF4: IFN regulatory factor 4; NFκB: nuclear factor kappa B; BATF: basic leucine zipper transcription factor; AHR: aryl hydrocarbon receptor; HIF-1A: hypoxia-inducible factor 1-alpha; Bcl6: B cell lymphoma 6; IL-12: interleukin-12; TGF-β: transforming growth factor-beta; T-bet: T-box transcription factor 21; GATA3: GATA binding protein 3; Foxp3: forkhead box P3
