CD49a regulates the function of human decidual natural killer cells

Am J Reprod Immunol. 2019 Apr;81(4):e13101. doi: 10.1111/aji.13101. Epub 2019 Mar 7.

Abstract

Problem: The function of CD49a on human decidual natural killer (dNK) cells is unknown.

Method of study: The expression of CD49a on dNK cells from human patients with recurrent spontaneous abortions or age-matched healthy controls was analyzed by flow cytometry. DNK cells were treated with CD49a neutralizing antibody and analyzed for function (cytokines production and cytotoxic activity). Long non-coding RNA (lncRNA) microarray analysis was used to identify a potential regulator of CD49a.

Results: DNK cells from human patients who underwent recurrent spontaneous abortions had lower levels of CD49a and increased perforin, granzyme B, and IFN-r expression, when compared to dNK cells from age-matched healthy controls. Perforin, granzyme B, and IFN-r expression levels in dNK cells were upregulated, while the migration and adhesion of dNK cells were downregulated by CD49a-neutralizing antibody. By the 51 Cr release assay, the killing activity of dNK cells also increased with CD49a neutralizing antibody. Further, lnc-49a, a newly identified lncRNA, was shown to be a positive regulator of CD49a in primary human NK cells.

Conclusion: CD49a is involved in the regulation of dNK cells functions, including cytotoxic activity, migration, and adhesion. Further, lnc-49a is a positive regulator of CD49a in human primary dNK cells.

Keywords: CD49a; adhesion; long non-coding RNAs; migration; natural killer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Spontaneous / immunology*
  • Adult
  • Antibodies, Neutralizing / metabolism
  • Cell Adhesion
  • Cell Movement
  • Cells, Cultured
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • Decidua / immunology*
  • Female
  • Gene Expression Regulation
  • Humans
  • Integrin alpha1 / immunology
  • Integrin alpha1 / metabolism*
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation
  • Pregnancy
  • RNA, Long Noncoding / genetics
  • Recurrence

Substances

  • Antibodies, Neutralizing
  • Cytokines
  • Integrin alpha1
  • RNA, Long Noncoding