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

BACKGROUND

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.

OBJECTIVES

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

METHODS

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 NOD mice, in which MyD88 is expressed only in CD11c cells.

RESULTS

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 NOD mice) restored hyper-CHS to a normal level in MyD88 NOD mice.

CONCLUSION

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