Indole-3-lactic acid ameliorates thrombocytopenia in primary immune thrombocytopenia by modulating the differentiation of Th17 and Tregs.

Abstract

Although some patients with primary immune thrombocytopenia (ITP) benefit from current treatments, there are still some refractory patients. Our previous research showed that the imbalance of the intestinal microbiota is associated with ITP. Indole-3-lactic acid (ILA) may act as a communication channel between the gut microbiota and the immune system. This study aimed to assess the ILA metabolism and the role in ITP. Plasma metabolites were measured by liquid chromatography-tandem mass spectrometry. Flow cytometry was used to analyse T-cell subsets and Fc gamma receptors on macrophages. Cytokine mRNA expression and plasma levels were detected by real-time quantitative polymerase chain reaction (qPCR) and a multiplex assay kit. An ITP mouse model was used to explore the effect of ILA on immune homeostasis. Newly diagnosed and refractory ITP patients with a deficiency of ILA and an imbalance of T helper cell type 17 (Th17)/regulatory T cells (Tregs). ILA alleviated thrombocytopenia in ITP mice by inhibiting Th17 differentiation and the expression of interleukin (IL)-1β, tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and IL-12/IL-23p40, and by promoting Tregs differentiation. ILA reduced Th17 cells, increased the Treg/Th17 ratio, downregulated IL17A and TNFα mRNA, and upregulated IL10 mRNA in refractory ITP patients. ILA ameliorates thrombocytopenia in ITP by modulating Th17/Tregs differentiation and suppressing TNF-α expression. Targeting ILA metabolism could be a promising therapeutic strategy for ITP.

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