SerpinB1 regulates homeostatic expansion of IL-17+ γδ and CD4+ Th17 cells

J Leukoc Biol. 2014 Mar;95(3):521-30. doi: 10.1189/jlb.0613331. Epub 2013 Nov 18.


SerpinB1 is an endogenous inhibitor of serine proteases recognized for its anti-inflammatory and host-protective properties. Although loss of serpinB1 in mice does not result in gross immune deregulation, serpinb1a(-/-) mice display increased mortality and inflammation-associated morbidity upon challenge with influenza virus. Here, we show that IL-17A(+) γδ and CD4(+) Th17 cells are already expanded in the lungs of serpinb1a(-/-) mice at steady-state. Both γδ and αβ(+) CD4(+) CCR6(+) T cells isolated from the lungs of naive serpinb1a(-/-) mice displayed a skewed transcriptional profile relative to WT cells, including increased Th17 signature transcripts [Il17a, l17f, and Rorc (RORγt)] and decreased Th1 signature transcripts [Ifng, Cxcr3, and Tbx21 (T-bet)] in γδ T cells. In addition to the lung, IL-17A(+) γδ and CD4(+) Th17 cells were increased in the spleen of naive serpinb1a(-/-) mice, despite normal αβ and γδ T cell development in the thymus. Within the γδ T cell compartment, loss of serpinb1a prompted selective expansion of Vγ4(+) and Vγ6/Vδ1(+) cells, which also displayed elevated expression of the proliferating cell nuclear antigen, Ki-67, and IL-17A. Given that serpinb1a is preferentially expressed in WT IL-17A(+) γδ and CD4(+) Th17 cell subsets vis-à-vis other T cell lineages, our findings reveal a novel function of serpinB1 in limiting untoward expansion of lymphocytes with a Th17 phenotype.

Keywords: cell proliferation; cytokine regulation; inflammation; lymphocytes; population size.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4 Antigens / immunology
  • Cell Proliferation
  • Female
  • Flow Cytometry
  • Homeostasis / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Orthomyxoviridae Infections / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Serpins / immunology*
  • T-Lymphocyte Subsets / immunology*
  • Th17 Cells / cytology
  • Th17 Cells / immunology*


  • CD4 Antigens
  • Receptors, Antigen, T-Cell, gamma-delta
  • Serpinb1a protein, mouse
  • Serpins