Impact of β2 integrin deficiency on mouse natural killer cell development and function

Karine Crozat, Céline Eidenschenk, Baptiste N. Jaeger, Philippe Krebs, Sophie Guia, Bruce Beutler, Eric Vivier, Sophie Ugolini

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Natural killer (NK) cells are innate immune cells that express members of the leukocyte β2 integrin family in humans and mice. These CD11/CD18 heterodimers play critical roles in leukocyte trafficking, immune synapse formation, and costimulation. The cell-surface expression of one of these integrins, CD11b/CD18, is also recognized as a major marker of mouse NK-cell maturation, but its function on NK cells has been largely ignored. Using N-ethyl-N-nitrosourea (ENU) mutagenesis, we generated a mouse carrying an A → T transverse mutation in the Itgb2 gene, resulting in a mutation that prevented the cell-surface expression of CD18 and its associated CD11a, CD11b, and CD11c proteins. We show that β2 integrin-deficient NK cells have a hyporesponsive phenotype in vitro, and present an alteration of their in vivo developmental program characterized by a selective accumulation of c-kit + cells. NK-cell missing-self recognition was partially altered in vivo, whereas the early immune response to mouse cytomegalovirus (MCMV) infection occurred normally in CD18-deficient mice. Therefore, β2 integrins are required for optimal NK-cell maturation, but this deficiency is partial and can be bypassed during MCMV infection, highlighting the robustness of antiviral protective responses.

Original languageEnglish (US)
Pages (from-to)2874-2882
Number of pages9
JournalBlood
Volume117
Issue number10
DOIs
StatePublished - Mar 10 2011

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Crozat, K., Eidenschenk, C., Jaeger, B. N., Krebs, P., Guia, S., Beutler, B., Vivier, E., & Ugolini, S. (2011). Impact of β2 integrin deficiency on mouse natural killer cell development and function. Blood, 117(10), 2874-2882. https://doi.org/10.1182/blood-2010-10-315457