Table 2.
Cell-intrinsic negative regulators of DC function in autoimmunity
| Protein deleted in DCs (gene targeted)* |
Disease phenotype | Mechanism of action | Refs |
|---|---|---|---|
| αVβ8 integrin (Itgb8) | Polyclonal immune activation, production of autoantibodies and development of colitis | DCs cannot activate latent TGFβ to induce regulatory T cell conversion | 42 |
| STAT3 (Stat3) | Cervical lymphadenopathy and ileocolitis | DCs are unresponsive to inhibitory signals delivered by IL-10 and they show enhanced induction of T cell priming and TH1 cell differentiation | 43 |
| BLIMP1 (Prdm1) | Increased germinal centre reaction, production of DNA-specific antibodies and development of SLE-like disease (females only) | Spontaneous production of IL-6 and the induction of T follicular helper cell differentiation by DCs | 44 |
| A20 (Tnfaip3) | Polyclonal immune activation, ankylosing arthritis and colitis | Spontaneous DC maturation, increased inflammatory cytokine production and enhanced T cell activation by DCs | 45 |
| Polyclonal immune activation and development of SLE-like disease | Reduced apoptosis and spontaneous maturation of DCs, increased inflammatory cytokine production by DCs, and increased uptake and presentation of apoptotic cells by DCs | 46 | |
| SHP1 (Ptpn6) | Polyclonal immune activation and development of SLE-like disease | Spontaneous DC maturation, and increased inflammatory cytokine production and induction of TH1 cell differentiation by DCs | 47,48 |
BLIMP1, B lymphocyte-induced maturation protein 1; DC, dendritic cell; IL, interleukin; SHP1, SH2 domain-containing protein tyrosine phosphatase 1; SLE, systemic lupus erythematosus; STAT3, signal transducer and activator of transcription 3; TGFβ; transforming growth factor-β; TH1, T helper 1.
*
Genes are shown that, when deleted in DCs using a DC-specific Cre-deleter mouse strain115, caused spontaneous inflammatory and/or autoimmune manifestations.