4.6 Article

α2β1 Integrin Is Required for Optimal NK Cell Proliferation during Viral Infection but Not for Acquisition of Effector Functions or NK Cell-Mediated Virus Control

Journal

JOURNAL OF IMMUNOLOGY
Volume 204, Issue 6, Pages 1582-1591

Publisher

AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1900927

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Funding

  1. National Institute of Allergy and Infectious Diseases (NIAID) [R01AI110457, R01AI065544]
  2. National Institute on Aging [AG048602]
  3. NIAID [T32 AI134646]
  4. University of Minho-School of Medicine - Fundacao para a Ciencia e Tecnologia [PD/BD/128078/2016]
  5. National Cancer Institute of the National Institutes of Health [P30CA056036]
  6. Fundação para a Ciência e a Tecnologia [PD/BD/128078/2016] Funding Source: FCT

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NK cells play an important role in antiviral resistance. The integrin alpha 2, which dimerizes with integrin beta 1, distinguishes NK cells from innate lymphoid cells 1 and other leukocytes. Despite its use as an NK cell marker, little is known about the role of alpha 2 beta 1 in NK cell biology. In this study, we show that in mice alpha 2 beta 1 deficiency does not alter the balance of NK cell/innate lymphoid cell 1 generation and slightly decreases the number of NK cells in the bone marrow and spleen without affecting NK cell maturation. NK cells deficient in alpha 2 beta 1 had no impairment at entering or distributing within the draining lymph node of ectromelia virus (ECTV)-infected mice or at becoming effectors but proliferated poorly in response to ECTV and did not increase in numbers following infection with mouse CMV (MCMV). Still, alpha 2 beta 1-deficient NK cells efficiently protected from lethal mousepox and controlled MCMV titers in the spleen. Thus, alpha 2 beta 1 is required for optimal NK cell proliferation but is dispensable for protection against ECTV and MCMV, two well-established models of viral infection in which NK cells are known to be important.

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