| First Author | Xu R | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 2 | Pages | 112054 |
| PubMed ID | 36724074 | Mgi Jnum | J:333443 |
| Mgi Id | MGI:7434058 | Doi | 10.1016/j.celrep.2023.112054 |
| Citation | Xu R, et al. (2023) TNFR2(+) regulatory T cells protect against bacteremic pneumococcal pneumonia by suppressing IL-17A-producing gammadelta T cells in the lung. Cell Rep 42(2):112054 |
| abstractText | Streptococcus pneumoniae is a pathogen of global morbidity and mortality. Pneumococcal pneumonia can lead to systemic infections associated with high rates of mortality. We find that, upon pneumococcal infection, pulmonary Treg cells are activated and have upregulated TNFR2 expression. TNFR2-deficient mice have compromised Treg cell responses and highly activated IL-17A-producing gammadelta T cell (gammadeltaT17) responses, resulting in significantly enhanced neutrophil infiltration, tissue damage, and rapid development of bacteremia, mirroring responses in Treg cell-depleted mice. Deletion of total Treg cells predominantly activate IFNgamma-T cell responses, whereas adoptive transfer of TNFR2(+) Treg cells specifically suppress the gammadeltaT17 response, suggesting a targeted control of gammadeltaT17 activation by TNFR2(+) Treg cells. Blocking IL-17A at early stage of infection significantly reduces bacterial blood dissemination and improves survival in TNFR2-deficient mice. Our results demonstrate that TNFR2 is critical for Treg cell-mediated regulation of pulmonary gammadeltaT17-neutrophil axis, with impaired TNFR2(+) Treg cell responses increasing susceptibility to disease. |
