Professor The University of Texas Health Science Center at Houston Houston, Texas, United States
Disclosure(s):
Yuying Liu, PhD: No financial relationships to disclose
Introduction/Rationale: Oral administration of probiotic Limosilactobacillus reuteri DSM 17938 prolongs survival and reduces Th1- and Th2-associated inflammation in Treg-deficient scurfy (SF) mice, which model human IPEX syndrome. It is unclear how DSM 17938 educated SF-CD4+T cells can facilitate T cell-liver communication.
Methods: We adoptively transferred by intraperitoneal injection cells isolated from SF spleens into lymphocyte-deficient-RAG1KO mice and compared the CD4+T cells from SF mice gavage-fed with DSM 17938 with the CD4+T cells from untreated SF mice (Prob-SF-CD4+T cells versus SF-CD4+T cells). Liver inflammatory histology and transcriptomes in RAG1KO mice were analyzed.
Results: We observed that Prob-SF-CD4+T cells reduced the incidence and severity of liver inflammation caused by transferring SF-CD4+T cells. SF-CD4+T cells up-regulated expression of liver genes involved in TLR cascades, inflammatory cytokine and death receptor signals, while down-regulated genes linked to mitochondrial respiratory chain complexes, TCA cycle, liver detoxification and lipid metabolism. However, Prob-SF-CD4+T cell transfer reversed SF-CD4+T cell-induced transcriptomic changes in inflammatory and metabolic clusters by modulating distinct genes participating in TLR regulation, mitochondrial function and cell cycle.
Conclusion: In conclusion, inflammatory CD4+T cells can perpetuate an exaggerated immune response in the immunologically naïve host. DSM17938 has the capacity to reprogram inflammatory CD4+T cells and allowed them to benefit the recipient. Probiotic-modulated T cells can be further explored as a therapeutic option for autoimmune liver diseases.
