Involvement of CD226+ NK cells in immunopathogenesis of systemic lupus erythematosus

Zhan Huang, Binqing Fu, Song Guo Zheng, Xiaomei Li, Rui Sun, Zhigang Tian, Haiming Wei

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Dysfunction of immune systems, including innate and adaptive immunity, is responsible for the immunopathogenesis of systemic lupus erythematosus (SLE). NK cells are a major part of the innate immune system, and diminished populations of NK cells have been reported in SLE patients. However, the mechanisms behind this decrease and the role of NK cells in SLE pathogenesis remain poorly understood. In this study, we found that a deficiency of NK cells, especially CD226+ NK cells, is prominent in patients with active SLE. Meanwhile, expression of the CD226 ligands CD112 and CD155 on plasmacytoid dendritic cells is observed in SLE patients; thus, activation of CD226+ NK cells may be induced by CD226-ligand interactions. Furthermore, IFN-α, which is mainly produced by plasmacytoid dendritic cells, can mediate the activation-induced cell death of NK cells. Therefore, these processes likely contribute to the loss of NK cells in patients with active SLE. Despite the impaired cytotoxicity of peripheral NK cells in human SLE patients and mouse SLE models, we provide evidence that CD226+ NK cells infiltrate the kidneys of predisease MRL-lpr/ lpr mice. Kidney-infiltrating NK cells displayed an activated phenotype and a marked ability to produce cytotoxic granules. These results suggest that, before apoptosis, activated NK cells can infiltrate tissues and, to some extent, mediate tissue injury by producing cytotoxic granules and immunoregulatory cytokines.

Original languageEnglish (US)
Pages (from-to)3421-3431
Number of pages11
JournalJournal of Immunology
Volume186
Issue number6
DOIs
StatePublished - Mar 15 2011

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Natural Killer Cells
Systemic Lupus Erythematosus
Dendritic Cells
Immune System
Ligands
Kidney
Adaptive Immunity
Innate Immunity
Cell Death
Apoptosis
Cytokines
Phenotype

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Huang, Z., Fu, B., Zheng, S. G., Li, X., Sun, R., Tian, Z., & Wei, H. (2011). Involvement of CD226+ NK cells in immunopathogenesis of systemic lupus erythematosus. Journal of Immunology, 186(6), 3421-3431. https://doi.org/10.4049/jimmunol.1000569
Huang, Zhan ; Fu, Binqing ; Zheng, Song Guo ; Li, Xiaomei ; Sun, Rui ; Tian, Zhigang ; Wei, Haiming. / Involvement of CD226+ NK cells in immunopathogenesis of systemic lupus erythematosus. In: Journal of Immunology. 2011 ; Vol. 186, No. 6. pp. 3421-3431.
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Huang, Z, Fu, B, Zheng, SG, Li, X, Sun, R, Tian, Z & Wei, H 2011, 'Involvement of CD226+ NK cells in immunopathogenesis of systemic lupus erythematosus', Journal of Immunology, vol. 186, no. 6, pp. 3421-3431. https://doi.org/10.4049/jimmunol.1000569

Involvement of CD226+ NK cells in immunopathogenesis of systemic lupus erythematosus. / Huang, Zhan; Fu, Binqing; Zheng, Song Guo; Li, Xiaomei; Sun, Rui; Tian, Zhigang; Wei, Haiming.

In: Journal of Immunology, Vol. 186, No. 6, 15.03.2011, p. 3421-3431.

Research output: Contribution to journalArticle

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