Regulation of contact sensitivity in non-obese diabetic (NOD) mice by innate immunity

Genetic background influences allergic immune responses to environmental stimuli. Non-obese diabetic (NOD) mice are highly susceptible to environmental stimuli. Little is known about the interaction of autoimmune genetic factors with innate immunity in allergies, especially skin hypersensitivity.

To study the interplay of innate immunity and autoimmune genetic factors in contact hypersensitivity (CHS) by using various innate immunity-deficient NOD mice.

Toll-like receptor (TLR) 2-deficient, TLR9-deficient and MyD88-deficient NOD mice were used to investigate CHS. The cellular mechanism was determined by flow cytometry in vitro and adoptive cell transfer in vivo. To investigate the role of MyD88 in dendritic cells (DCs) in CHS, we also used CD11c^MyD88+  MyD88^-/- NOD mice, in which MyD88 is expressed only in CD11c⁺ cells.

We found that innate immunity negatively regulates CHS, as innate immunity-deficient NOD mice developed exacerbated CHS accompanied by increased numbers of skin-migrating CD11c⁺ DCs expressing higher levels of major histocompatibility complex II and CD80. Moreover, MyD88^-/- NOD mice had increased numbers of CD11c⁺  CD207^-  CD103⁺ DCs and activated T effector cells in the skin-draining lymph nodes. Strikingly, re-expression of MyD88 in CD11c⁺ DCs (CD11c^MyD88+  MyD88^-/- NOD mice) restored hyper-CHS to a normal level in MyD88^-/- NOD mice.

Our results suggest that the autoimmune-prone NOD genetic background aggravates CHS regulated by innate immunity, through DCs and T effector cells.