Environmental factors determine DAP12 deficiency to either enhance or suppress immunopathogenic processes

Area of Science:

• Immunology
• Ophthalmology
• Genetics

Background:

• DNAX-activation protein 12 (DAP12) is a key adapter molecule in immune signaling pathways.
• DAP12 and its associated receptors are expressed in ocular tissues.
• The role of DAP12 in autoimmune diseases, including experimental autoimmune uveitis (EAU), remains unclear.

Purpose of the Study:

• To investigate the influence of DAP12 deficiency on the development of EAU.
• To determine how environmental factors might modulate the effects of DAP12 deficiency on autoimmune responses.

Main Methods:

• Quantitative RT-PCR to assess gene expression of DAP12 and its receptors in mouse eyes.
• Induction of EAU in DAP12-deficient and wild-type mice housed in different animal facilities.
• In vitro stimulation of lymphocytes with interphotoreceptor retinoid-binding protein (IRBP) to analyze proliferation and cytokine profiles.

Main Results:

• Initial studies in one facility suggested enhanced EAU in DAP12-deficient mice.
• Upon re-derivation to a cleaner facility, DAP12-deficient mice became hyporesponsive to EAU induction.
• Lymphocytes from DAP12-deficient mice exhibited distinct cytokine profiles depending on the housing environment, with opposite pro- and anti-inflammatory responses observed between facilities.

Conclusions:

• The impact of DAP12 deficiency on experimental autoimmune uveitis is profoundly influenced by environmental factors.
• These findings highlight the critical role of the animal facility environment in modulating immune responses and disease development.