To investigate the role of Nod2 in susceptibility to the autoimmune disease, type 1 diabetes mellitus (T1DM), we generated Nod2<sup>-/-</sup> non-obese diabetic (NOD) mice.
Recent studies have uncovered unexpected functions of NOD2 in innate immune responses such as induction of type I interferon and facilitation of autophagy; moreover, they have disclosed extensive cross-talk between NOD2 and Toll-like receptors, which has an indispensable role both in host defense against microbial infection and in the development of autoimmunity.
Whether a distorted balance between the function of Nod1 and/or Nod2 is involved in the pathogenesis of human autoinflammatory or autoimmune disease, such as rheumatoid arthritis, remains to be elucidated.
Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is regarded with other molecules such as HLA, PTPN22 and CARD15 as genetic master switches of autoimmunity.
Based on its position on chromosome 16 coincident with some other autoimmune disease susceptibility localizations, research has targeted NOD2 variation as the potential cause of other autoimmune disorders.
Genetic variants of CARD15 that might result in inappropriate immunomodulation are not only associated with autoimmune diseases but also with atopic disorders.