Serpinb1a Is Dispensable for the Development and Cytokine Response of Invariant Natural Killer T Cell Subsets

Front Immunol. 2020 Nov 11;11:562587. doi: 10.3389/fimmu.2020.562587. eCollection 2020.

Abstract

Invariant natural killer T (iNKT) cells are innate-like T lymphocytes. They quickly respond to antigenic stimulation by producing copious amounts of cytokines and chemokines. iNKT precursors differentiate into three subsets iNKT1, iNKT2, and iNKT17 with specific cytokine production signatures. While key transcription factors drive subset differentiation, factors that regulate iNKT subset homeostasis remain incompletely defined. Transcriptomic analyses of thymic iNKT subsets indicate that Serpinb1a is one of the most specific transcripts for iNKT17 cells suggesting that iNKT cell maintenance and function may be regulated by Serpinb1a. Serpinb1a is a major survival factor in neutrophils and prevents cell death in a cell-autonomous manner. It also controls inflammation in models of bacterial and viral infection as well as in LPS-driven inflammation. Here, we examined the iNKT subsets in neutropenic Serpinb1a -/- mice as well as in Serpinb1a -/- mice with normal neutrophil counts due to transgenic re-expression of SERPINB1 in neutrophils. In steady state, we found no significant effect of Serpinb1a-deficiency on the proliferation and numbers of iNKT subsets in thymus, lymph nodes, lung, liver and spleen. Following systemic activation with α-galactosylceramide, the prototypic glycolipid agonist of iNKT cells, we observed similar serum levels of IFN-γ and IL-4 between genotypes. Moreover, splenic dendritic cells showed normal upregulation of maturation markers following iNKT cell activation with α-galactosylceramide. Finally, lung instillation of α-galactosylceramide induced a similar recruitment of neutrophils and production of iNKT-derived cytokines IL-17, IFN-γ, and IL-4 in wild-type and Serpinb1a -/- mice. Taken together, our results indicate that Serpinb1a, while dominantly expressed in iNKT17 cells, is not essential for iNKT cell homeostasis, subset differentiation and cytokine release.

Keywords: cytokine response; innate immunity; invariant NKT; serpin; α-galactosylceramide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cytokines / metabolism*
  • Dendritic Cells / immunology
  • Female
  • Galactosylceramides / adverse effects
  • Homeostasis / genetics
  • Inflammation / chemically induced
  • Inflammation / immunology
  • Inflammation / metabolism
  • Liver / immunology
  • Lung / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Natural Killer T-Cells / immunology*
  • Neutrophils / immunology
  • Serpins / deficiency*
  • Serpins / genetics
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*
  • Spleen / immunology

Substances

  • Cytokines
  • Galactosylceramides
  • Serpinb1a protein, mouse
  • Serpins
  • alpha-galactosylceramide