| First Author | Zhao P | Year | 2014 |
| Journal | J Leukoc Biol | Volume | 95 |
| Issue | 3 | Pages | 521-30 |
| PubMed ID | 24249741 | Mgi Jnum | J:211841 |
| Mgi Id | MGI:5576460 | Doi | 10.1189/jlb.0613331 |
| Citation | Zhao P, et al. (2014) SerpinB1 regulates homeostatic expansion of IL-17+ gammadelta and CD4+ Th17 cells. J Leukoc Biol 95(3):521-30 |
| abstractText | 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(+) gammadelta and CD4(+) Th17 cells are already expanded in the lungs of serpinb1a(-/-) mice at steady-state. Both gammadelta and alphabeta(+) 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 (RORgammat)] and decreased Th1 signature transcripts [Ifng, Cxcr3, and Tbx21 (T-bet)] in gammadelta T cells. In addition to the lung, IL-17A(+) gammadelta and CD4(+) Th17 cells were increased in the spleen of naive serpinb1a(-/-) mice, despite normal alphabeta and gammadelta T cell development in the thymus. Within the gammadelta T cell compartment, loss of serpinb1a prompted selective expansion of Vgamma4(+) and Vgamma6/Vdelta1(+) 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(+) gammadelta and CD4(+) Th17 cell subsets vis-a-vis other T cell lineages, our findings reveal a novel function of serpinB1 in limiting untoward expansion of lymphocytes with a Th17 phenotype. |
