Kazachstania pintolopesii triggers an immune-endothelial-fibroblast cascade and drives inflammatory arthritis and tissue fibrosis in genetically susceptible hosts

Diling Chen^1*Haiting Zhang²Lei Li²Duanling Tan¹Chulan Lin²Yanqing Zhang²

• ¹Guangdong Yier Biotechnology Co., LTD, Guangzhou, China
• ²the Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China

There is growing evidence that the microbiota plays a crucial role in the onset of numerous autoimmune diseases, although direct evidence linking specific microorganisms to particular autoimmune conditions remains limited. Our previous experiments identified Kazachstania pintolopesii that a characteristic fungus isolated from spontaneous ankylosing spondylitis (AS) monkeys as an inducer of PANoptosome assembly, though the underlying mechanism remained unclear. This study enhances our understanding of how environmental fungi such as K. pintolopesii disrupt immune homeostasis via multicellular crosstalk, metabolic reprogramming, and dysregulated cytokine networks. Furthermore, we elucidate how lysates of K. pintolopesii trigger an immune-endothelial-fibroblast cascade that drives inflammatory arthritis and tissue fibrosis in genetically susceptible hosts. By deciphering these pathways, we identify potential therapeutic targets to disrupt this pathogenic network and alleviate autoimmune pathology.