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Lemoinne, S.

Publications and source records attributed to Lemoinne, S..

3 recordsLinked to original sources
bioRxiv2025

Clonal analysis of SepSecS-specific CD4 T cells reveals a new HLA-DPA1*02:01/HLA-DPB1*01:01-restricted immunodominant epitope in autoimmune hepatitis

Autoreactive CD4 T cells, recognizing liver-self-antigens such as SepSecS, are main drivers of the chronic inflammatory response during autoimmune hepatitis (AIH). Previous studies have uncovered immunodominant SepSecS epitopes often associated with HLA-DRB1*03 or HLA-DRB1*04 restriction, two alleles enriched in AIH population. However, HLA restriction of numerous SepSecS epitopes remains incomplete and it is still unclear if immunodominant epitopes could be presented by non-HLA-DR molecules. Here, we investigated epitope recognition of SepSecS-specific TCRs isolated from AIH patients, and their HLA restriction by generating TCR hybridoma cell lines. Seventeen TCRs recognized eight SepSecS epitopes with four distinct HLA restrictions, including a novel HLA-DPA1*02:01/DPB1*01:01-restricted SepSecS epitope. TCR clustering analysis using GLIPH2 algorithm suggested that this epitope is recognized by multiple distinct TCRs in HLA-DPA1*02:01[~]HLA-DPB1*01:01 patients. Our study provides new insights into liver-self-antigen T cell reactivity during AIH, which could offer potential therapeutic strategies by targeting autoreactive CD4 T cells.

immunology↗
bioRxiv2025

Accumulation of PD-1+ TIGIT+ T cells in the liver after local antigen reactivity and during autoimmune hepatitis

In autoimmune hepatitis (AIH), hepatocellular damage is linked to an accumulation of autoreactive T cells in the liver of patients, but how these cells emerge in the tissue remains unclear. Here we used a mouse model based on recombination-dependent inducible expression of influenza A hemagglutinin (HA) by hepatocytes to investigate initiation of liver antigen-specific response. Our study revealed that peripheral immunization, unlike inflammatory triggers, is essential to initiate an immune response against a liver antigen. We showed that liver T cell reactivity after peripheral immunization is marked by PD-1 and TIGIT co-expression and that the frequency of PD-1+ TIGIT+ HLA-DR+ CD38+ CD8 T cells in the blood of AIH patients is associated with liver injury. Our findings suggest a potential influence of the peripheral immunization for the liver-antigen-specific responses during AIH. Liver tissue-activated T cells probably recirculate during active phase of the disease, unveiling potential immunomarkers to monitor disease activity. HighlightsO_LIPeripheral immunization rather than local inflammation induces an immune response against a hepatic antigen C_LIO_LIPD-1 and TIGIT co-expression by T cells is found after tissue antigen-specific T cell reactivity C_LIO_LIFrequency of circulating PD-1+ TIGIT+ HLA-DR+ CD38+ CD8 T cells is associated with AIH disease activity C_LI In briefGuinebretiere et al. demonstrate that after peripheral immunization, liver-antigen-specific T cell accumulation in the tissue is marked by local PD-1/TIGIT co-expression, a phenotype shared with liver and circulating T cell subsets enriched in active autoimmune hepatitis (AIH) patients. These findings suggest the influence of peripheral immunization on the initiation of AIH and provide potential immunomarker of AIH activity.

immunology↗
bioRxiv2023

Hepatic stellate cells maintain liver homeostasis through paracrine neurotrophin-3 signaling

Organ homeostasis is maintained by regulated proliferation of distinct cell populations. In mouse liver, cyclin D1-positive hepatocytes in the midlobular zone repopulate the parenchyma at a constant rate to preserve liver homeostasis. The mitogenic cues that underlie this process are unknown. Hepatic stellate cells, the livers pericytes, are in close proximity to hepatocytes and have been implicated in supporting hepatocyte proliferation, but their role in liver homeostasis is unknown. Here, we employ a T cell-mediated hepatic stellate cell ablation model to remove nearly all hepatic stellate cells in the murine liver, enabling the unbiased characterization of hepatic stellate cell functions. In the normal murine liver, complete loss of hepatic stellate cells persists for up to 6 weeks and reduces liver mass. Our results show that hepatic stellate cells induce cyclin D1 in midlobular hepatocytes by release of neurotrophin-3 to promote hepatocyte proliferation via tropomyosin receptor kinase B signaling. These findings establish that hepatic stellate cells form the niche for midlobular hepatocytes and reveal a novel hepatocyte growth factor signaling pathway. One-Sentence SummaryHepatic stellate cells provide mitogenic cues for midlobular hepatocyte proliferation and metabolic zonation by secreting neurotrophin-3.

cell biology↗