SLAMF9 activation by Akkermansia muciniphila-derived lipid LPE(16:0) drives IL-10+ B cell-mediated protection against ulcerative colitis

  1. Ye Chen
  2. Huiping Yang
  3. Xuefeng Gao
  4. Haolin Li
  5. Shuze Chen
  6. Lu Lin
  7. Lei Mai
  8. Ying Wang
  9. Xiuying Liu
  10. Qiujuan Ye
  11. Xiaofeng Li
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Abstract

Ulcerative colitis (UC) pathogenesis involves aberrant interactions between the intestinal microbiota and immune system, notably reduced IL-10-producing B cells and diminished Akkermansia muciniphila (Akk). Probiotic extracellular vesicles (EVs) offer safety and transferability advantages over live bacteria. Here, we demonstrate that EVs from A. muciniphila (AkkEVs) reduce DSS-induced colitis by expanding IL-10+ B220+ cells. Lipidomics identified lysophosphatidylethanolamine (LPE(16:0)) as a lipid specifically enriched in AkkEVs. Mechanistically, LPE(16:0) binds SLAMF9 on B cells, activating the SAP/VAV1/ERK pathway to enhance IL-10 production and ameliorate colitis. Thus, AkkEVs and their derived lipid LPE(16:0) are novel SLAMF9 agonist and a candidate therapeutic for UC.

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  1. Version published to 10.21203/rs.3.rs-8143103/v1 on Research Square