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

Vanessa Montalvo, Laura Quigley, Barbara P. Vistica, Kimberly C. Boelte, Lindsey F. Nugent, Toshiyuki Takai, Daniel W. Mcvicar, Igal Gery

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

DNAX-activation protein 12 (DAP12), a transmembrane adapter, plays a major role in transducing activation signals in natural killer cells and various myeloid cells. Quantitative RT-PCR detected in normal mouse eyes considerable levels of DAP12 and multiple DAP12-coupled receptors, in particular TREM-1, Clec5a and SIRPb1. The role of DAP12 and its receptors in experimental autoimmune diseases has been controversial. Here, we analysed the effect of DAP12 deficiency on the capacity of mice to mount immunopathogenic cellular responses to the uveitogenic ocular antigen and interphotoreceptor retinoid-binding protein (IRBP), and to develop experimental autoimmune uveitis (EAU). Surprisingly, sequential analysis of EAU in mice deficient in DAP12 in two different animal facilities at first revealed enhanced disease as compared with wild-type mice, but when these mice were re-derived into a second, cleaner, animal facility, the response of control mice was essentially unchanged, whereas the DAP12 null mice were markedly hyporesponsive relative to controls in the new facility. Accordingly, when stimulated in vitro with IRBP, lymphocytes from the DAP12-deficient mice housed in the two facilities proliferated and produced opposite profiles of pro-inflammatory and anti-inflammatory cytokines, compared with their controls. These findings therefore demonstrate that the effects of DAP12 deficiency on development of autoimmune disease are dramatically affected by environmental factors. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Original languageEnglish
Pages (from-to)475-482
Number of pages8
JournalImmunology
Volume140
Issue number4
DOIs
Publication statusPublished - 2013 Dec

Keywords

  • Cytokines
  • Lymphoid cells
  • Ocular inflammation
  • TREM-2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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