Table 2.
Compacted rules and steady states associated to differentiation to functional cell subsets: Th1, Th2, Treg, and Th17.
| Node | Interactive rule | Steady state |
|---|---|---|
| Th1 | ||
| IL12e | Input | 1 |
| IFNGe | Input | 1 |
| TBET | MTORC1 and NFKB and NFAT and AP1 | TCR and CD28 and not AMPK |
| and IL12e and IFNGe | ||
| IFNG | TBET and AP1 and NFAT | TCR and CD28 and not AMPK |
| Th2 | ||
| IL4e | Input | 1 |
| GATA3 | MTORC2 and STAT5 and NFAT and IL4e | TCR and CD28 and AMPK |
| IL4 | GATA3 | TCR and CD28 and AMPK |
| Treg | ||
| TGFBe | Input | 1 |
| IL10e | Input | 1 |
| FOXP3 | (AMPK and NFAT and STAT5 and AP1 | TCR and CD28 and AMPK |
| and IL2G and TGFBe and IL10e) or | ||
| (IL10 and TGFBe and IL10e and CTLA4) | ||
| or (TGFB and TGFBe) | ||
| IL10 | FOXP3 and TGFBe | TCR and CD28 and AMPK |
| TGFB | FOXP3 | TCR and CD28 and AMPK |
| Th17 | ||
| TGFBe | Input | 1 |
| IL21e | Input | 1 |
| RORGT | CD28 and MTORC1 and IL12e and TGFBe | TCR and CD28 an not AMPK |
| IL21 | IL21e or RORGT | TCR and CD28 an not AMPK |
| IL17 | RORGT | TCR and CD28 and not AMPK |
In each case, it has been assumed that exogenous cytokines defining a specific microenvironment are expressed, while the rest is absent. The respective microenvironments correspond to IL12e and IFNGe (Th1), IL4e (Th2), TGFBe and IL10e (Treg), and TGFBe and IL21e (Th17). Besides exogenous cytokine expression, each steady state requires the activation of TCR and CD28, in other words, requires the expression of the activation core. AMPK acts like a switch promoting either cytotoxic or inflammatory immune responses (Th1 or Th17), or alternatively, humoral or regulatory responses (Th2 or Treg).