MMP12 exacerbates pulmonary inflammation by enhancing IL-17A expression

Mycoplasma pneumoniae is a major cause of pediatric community-acquired respiratory infections, accounting for approximately 50% of non-bacterial pneumonia cases. Although the symptoms of M. pneumoniae infection are generally mild and self-limited, about 25% of patients are hospitalized because of severe pneumonia or extrapulmonary complications. Community-acquired respiratory distress syndrome (CARDS) toxin, an adenosine diphosphate–ribosylating and vacuolating cytotoxin, is a key virulence factor produced by M. pneumoniae. While previous studies have reported that CARDS toxin regulates pulmonary inflammatory responses via the KELED sequence, the underlying molecular mechanisms remain incompletely understood.

Recently, a research team led by Jieqiong Li, Nan Song, and Zhaohui Tong from Beijing Chaoyang Hospital, Capital Medical University, published a research article entitled “MMP12 exacerbates pulmonary inflammation by enhancing IL-17A expression” in hLife. The study revealed that matrix metalloproteinase 12 (MMP12) aggravates pulmonary inflammation by promoting interleukin-17A (IL-17A) expression.

This finding demonstrates that CARDS toxin exposure markedly increases the abundance of Mmp12^high macrophages in the murine lung, which was associated with overactivation of pro-inflammatory cytokine signaling. Macrophage-specific Mmp12 knockout attenuated CARDS toxin-induced pulmonary inflammation. Mechanistically, MMP12 protein promoted T helper 17 cells activation and subsequent IL-17A secretion via SPP1 and FN1, thereby exacerbating pulmonary inflammation. Notably, IL-17A blockade significantly mitigated these responses.

“Our findings establish a critical proinflammatory axis involving MMP12 and IL-17A that mediates CARDS toxin-induced pulmonary pathology, uncovering potential therapeutic targets for mitigating M. pneumoniae-associated respiratory disease,” said Jieqiong Li, Ph.D.

This work was conducted by researchers at Beijing Chaoyang Hospital, Capital Medical University. Support was provided by the Beijing Natural Science Foundation, National Natural Science Foundation of China, Beijing Hospitals Authority Clinical Medicine Development Special Funding Support, and the Reform and Development Program of Beijing Institute of Respiratory Medicine.

About Author:

Dr. Jieqiong Li is a full professor in the Beijing Chaoyang Hospital, Capital Medical University, China. Her research interests focus on multi-omics analysis and host anti-infective mechanism studies in respiratory infectious diseases. Until now, she has published more than 25 SCI papers in high-impact, peer-reviewed journals in the field, including Critical Care (2 papers), Emerging Microbes & Infections, and BMC Medicine. For more information, please pay attention to her research homepage https://www.bjcyh.com.cn/Html/Doctors/Main/Index_100003.html.