Figure 1.

Yin-Yang concept of autoimmunity: The type of autoimmune reaction that DCs induce when presenting antigen to T cells depends on environmental signals they receive through innate pattern recognition receptors. In the homeostatic situation (scenario 1; no disease) antigen is sampled from the environment in the absence of danger; i.e. inhibitory signals received via CLRs are in balance with activating signals via TLRs. The APCs remain in an immature/tolerogenic state that induces Treg → no disease (b). When antigen is recognised in the context of danger signals relayed through TLRs (scenario 2; transient autoimmunity), the DCs mature to an immunogenic state that activates autoaggressive T cells. When the danger has been cleared homeostasis is restored; newly formed Treg cells dampen autoimmune process. When scenario 2 occurs in individuals with a glycosylation defect, restoration of homeostasis and disease remission cannot occur (scenario 3; chronic autoimmunity). DCs: dendritic cells; CLRs: C-type lectin receptors; TLRs: Toll-like receptors; APCs: antigen-presenting cells; Treg: regulatory T cells.