The Ammonia-Slc4a11 axis in T cells alleviates LPS-Induced Mastitis

Lei Zhu^1*Yuqing Wu^2,3Zhi Li⁴Peiwen Xi⁵Yaman Wang^2,3Haowei Guo¹Hong Yin^1*

• ¹Nanjing Women and Children’s HealthCare Hospital, Nanjing, China
• ²Department of Laboratory Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China
• ³Branch of National Clinical Research Center for Laboratory Medicine, Nanjing, Liaoning Province, China
• ⁴Huai'an First People's Hospital, Huai'an, Jiangsu, China
• ⁵First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China

Mastitis, an inflammation of the mammary gland, is a prevalent condition among lactating and non-puerperal women, posing significant health challenges and economic burdens. Lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, is a principal inducer of mastitis. While ammonia, a critical molecule in body nitrogen metabolism, has been implicated in inflammatory pathways, its specific role in mastitis has been unclear. This study aimed to elucidate the mechanism of ammonia in mastitis development using mouse models. Our findings demonstrate that ammonia can inhibit LPS-induced mastitis, reduce T cell activity, and decrease the expression of inflammatory factors. Notably, ammonia regulates T cell activity to suppress mastitis progression. Furthermore, we discovered that knockdown of the Slc4a11 gene, which is implicated in ammonia transport, exacerbates LPS-induced mastitis, suggesting that Slc4a11 plays a role in modulating mastitis progression through T cells. In conclusion, our results offer novel insights into the pathogenesis of mastitis and lay the theoretical groundwork for the development of ammonia and T cell-based therapeutic strategies. Future research is necessary to validate these findings in clinical samples and to delve deeper into the mechanisms of ammonia and the Slc4a11 gene, thereby advancing the treatment of mastitis.