Constitutive retinal CD200 expression regulates resident microglia and activation state of inflammatory cells during experimental autoimmune uveoretinitis

C. Broderick, R. M. Hoek, John Vincent Forrester, Janet Mary Liversidge, J. D. Sedgwick, A. D. Dick

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

Recent evidence supports the notion that tissue OX2 (CD200) constitutively provides down-regulatory signals to myeloid-lineage cells via CD200-receptor (CD200R). Thus, mice lacking CD200 (CD200(-/-)) show increased susceptibility to and accelerated onset of tissue-specific autoimmunity. In the retina there is extensive expression of CD200 on neurons and retinal vascular endothelium. We show here that retinal microglia in CD200(-/-) mice display normal morphology, but unlike microglia from wild-type CD200(+/+) mice are present in increased numbers and most significantly, express inducible nitric oxide synthase (NOS2), a macrophage activation marker. Onset and severity of uveitogenic peptide (1-20) of interphotoreceptor retinoid-binding protein-induced experimental autoimmune uveoretinitis is accelerated in CD200(-/-) mice and although tissue destruction appears no greater than seen in CD200(+/+) mice, there is continued increased ganglion and photoreceptor cell apoptosis. Myeloid cell infiltrate was increased in CD200(-/-) mice during experimental autoinimune uveoretinitis, although NOS2 expression was not heightened. The results indicate that the CD200:CD200R axis regulates retinal microglial activation. In CD200(-/-) mice the release of suppression of tonic macrophage activation, supported by increased NOS2 expression in the CD200(-/-) steady state accelerates disease onset but without any demonstration of increased target organ/tissue destruction.

Original languageEnglish
Pages (from-to)1669-1677
Number of pages8
JournalAmerican Journal of Pathology
Volume161
Issue number5
Publication statusPublished - 2002

Keywords

  • BINDING PROTEIN
  • MACROPHAGES
  • RAT
  • DIFFERENTIATION
  • ANTIGENS
  • RECEPTOR
  • MICE
  • IDENTIFICATION
  • HETEROGENEITY
  • PROLIFERATION

Cite this

Broderick, C., Hoek, R. M., Forrester, J. V., Liversidge, J. M., Sedgwick, J. D., & Dick, A. D. (2002). Constitutive retinal CD200 expression regulates resident microglia and activation state of inflammatory cells during experimental autoimmune uveoretinitis. American Journal of Pathology, 161(5), 1669-1677.

Constitutive retinal CD200 expression regulates resident microglia and activation state of inflammatory cells during experimental autoimmune uveoretinitis. / Broderick, C.; Hoek, R. M.; Forrester, John Vincent; Liversidge, Janet Mary; Sedgwick, J. D.; Dick, A. D.

In: American Journal of Pathology, Vol. 161, No. 5, 2002, p. 1669-1677.

Research output: Contribution to journalArticle

Broderick, C, Hoek, RM, Forrester, JV, Liversidge, JM, Sedgwick, JD & Dick, AD 2002, 'Constitutive retinal CD200 expression regulates resident microglia and activation state of inflammatory cells during experimental autoimmune uveoretinitis', American Journal of Pathology, vol. 161, no. 5, pp. 1669-1677.
Broderick, C. ; Hoek, R. M. ; Forrester, John Vincent ; Liversidge, Janet Mary ; Sedgwick, J. D. ; Dick, A. D. / Constitutive retinal CD200 expression regulates resident microglia and activation state of inflammatory cells during experimental autoimmune uveoretinitis. In: American Journal of Pathology. 2002 ; Vol. 161, No. 5. pp. 1669-1677.
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