Characterization of MHC-II expressing FRCs in steady state and inflammatory conditions

Activity: Talk or presentationOral presentation

Description

Lymph node stromal cells (LNSCs) are key modulators of the immune response, forming the LN structure and producing crucial factors for lymphocyte migration and survival. LNSCs can be divided in four main subsets: fibroblastic reticular cells (FRCs), lymphatic and blood endothelial cells (LECs and BECs) and double negative cells (DNs). Recently, it has become clear that these populations serve as a reservoir of peripheral tissue antigens and contribute to the maintenance of peripheral tolerance. The K14ova mouse model can be exploited to study this function since keratinocyte-14 promoter driven transgenic expression of ovalbumine (ova) in the skin of these mice results in ova expression by LECs and FRCs in skin draining LNs, with no ova expression detected in dendritic cells. Benefiting from this model, we have previously demonstrated that presentation of self-antigens via MHC-II by LNSCs mediates conversion of antigen-specific T cells into CD25+ FoxP3+ regulatory T cells (Tregs). Here, we have addressed the tolerogenic function of LNSCs during inflammation. In vitro stimulation of K14ova LNSCs with lipopolysaccharide (LPS) reduced ova expression and hampered the conversion of naïve T cells into Tregs. Similarly, post LPS injection, LNSCs from K14ova mice upregulated MHC-II, while ova expression was downregulated. Hence, our data suggests that MHC-II+ LECs and FRCs induce the conversion of self-antigen reactive naïve T cells to Tregs under steady state but not during inflammatory conditions. To further characterize these cells, we have sorted MHC-II+ and MHC-II- FRCs from wild type mice and performed single cell RNA sequencing analysis. Our data indicates that MHC-II expressing FRCs are an heterogeneous population where Bst1 FRCs have the highest potential to present self-antigens via MHC-II in steady state conditions.
Period20 Feb 2020
Event titleKeystone symposium: Stromal Cells in Immunity and Disease
Event typeConference
LocationVictoria, Canada
Degree of RecognitionInternational