Table 1.
Key signaling molecules of intrathymic cellular network.
| Molecule | Cell expression | Functions in thymus | References |
|---|---|---|---|
| CD205 | cTECs | Apoptopic cell clearance | (71) |
| β5t | cTECs, TEPCs | Thymic proteosome component, CD8+ T cell selection | (71) |
| PRSS16 | cTECs | Thymus specific serine protease, CD4+ selection | (71) |
| DLL4 | cTECs | Notch ligand, regulator of T cell commitment and β selection | (71) |
| CXCL12 | cTECs | Chemokine ligand for CXCR4, regulation of β selection | (71) |
| CCL21 | mTECs | Chemokine ligand for CCR7, regulator of cortex to medulla migration of SP thymocytes | (71) |
| CCL25 | cTECs, mTECs | Chemokine ligand for CCR9, recruitment and positioning of TLPs, regulator of CD4+CD8+ thymocyte migration | (71) |
| LTβR | cTECs, mTECs | Ligand for lymphotoxin, regulator of mTEC and thymic endothelium development | (71) |
| Aire | mTECs | Tissue restricred antigen expression, tolerance | (71) |
| Fezf2 | mTECs | Tissue restricred antigen expression, tolerance | (71) |
| RANK | mTECs, mTEPCs | mTEC development | (71) |
| Relb | mTECs | mTEPC development | (71) |
| IFNγ | Activated T cells, NK cells | T cell maturation and differentiation | (6) |
| SCF | cTECs | Maintenance of TLPs | (71) |
| THGF | Self-renewing TLPs | Activation and proliferation of self- renewing TLPs |
(36, 152, 153) |
| IL-1 | TECs, Macrophages | T cell activation and growth | (6) |
| IL-2 | Activated T cells | T cell activation and development | (6) |
| IL-4 | Activated T cells | T cell growth factor | (6) |
| IL-6 | Macrophages, fibroblasts | T cell maturation and development | (6) |
| IL-7 | cTECs and mTECs in adult thymus, TEPCs in embryonic thymus, stromal cells, DCs | Proliferation of TLPs | (6, 71) |
| IL-9 | Activated T cells | T cell growth factor | (6) |
| IL-12 | T cells | Maintenance of thymus integrity and function | (6) |
| IL-15 | mTECs | Regulation of iNKT cells | (71) |
| IL-17 | T cells | Activation of CD4+ T cells, production of Treg17 cells | (6) |
| IL-21 | Activated CD4+ T cells | Differentiation of CD4+ T cells, development of Treg17 cells | (6) |
| IL-22 | Th17 cells, γδ T cells, NKT cells, ILCs | Proliferation and survival of TECs, Thymus regeneration | (6, 142, 143) |
| IL-25 | Thymic tuft cells | Regulation of intrathymic ILCs and iNKT cells | (71) |
| TGFβ | Activated T cells | Inhibition of IL-1-, IL-2- and IL-7-dependent proliferation of thymocytes | (6) |
| TNFα | Macrophages | Promotion of T cell proliferation | (6) |
| TSLP | TECs, DCs | Promotion of Th2 cell differentiation of CD4+ naïve T cells, activation of ILCs | (6) |
DLL4, Delta like 4; LTβR, Lymphotoxin beta Receptor; Aire, Autoimmune Regulator; RANK, Receptor Activator of Nuclear Factor κB; ILCs, Innate Lymphoid Cells; iNKT, invariant Natural Killer T Cells; SP, Single Positive; DCs, Dendritic Cells; cTECs, cortical Thymic Epithelial Cells; mTECs; medullary Thymic Epithelial Cells; TEPCs, Thymic Epithelial Progenitor Cells; TLPs, Thymic Lymphocite Progenitors; Th, T helper; Treg, T regulator; IFNγ, Interferon gamma; SCF, Stem Cell Factor; THGF, Thymocyte Growth Factor; IL, Interleukin; TGFβ, Transforming Growth Factor beta; TNFα, Tumor Necrosis Factor alpha; TSLP, Thymic Stromal Lymphopoietin.