The co-inhibitory receptor TIGIT regulates NK cell function and is upregulated in human intrahepatic CD56 NK cells.

The crosstalk between NK cells and their surrounding environment is enabled through activating and inhibitory receptors, which tightly control NK cell activity. The co-inhibitory receptor TIGIT decreases NK cell cytotoxicity and is involved in NK cell exhaustion, but has also been associated with liver regeneration, highlighting that the contribution of human intrahepatic CD56 NK cells in regulating tissue homeostasis remains incompletely understood. A targeted single-cell mRNA analysis revealed distinct transcriptional differences between matched human peripheral blood and intrahepatic CD56 NK cells.

Sex differences in the percentage of IRF5 positive B cells are associated with higher production of TNF-α in women in response to TLR9 in humans.

Background: The clinical course and outcome of many diseases differ between women and men, with women experiencing a higher prevalence and more severe pathogenesis of autoimmune diseases. The precise mechanisms underlying these sex differences still remain to be fully understood. IRF5 is a master transcription factor that regulates TLR/MyD88-mediated responses to pathogen-associated molecular patterns (PAMPS) in DCs and B cells.

Single-cell atlas of hepatic T cells reveals expansion of liver-resident naive-like CD4 T cells in primary sclerosing cholangitis.

Background & Aims: Little is known about the composition of intrahepatic immune cells and their contribution to the pathogenesis of primary sclerosing cholangitis (PSC). Herein, we aimed to create an atlas of intrahepatic T cells and thereby perform an in-depth characterization of T cells in inflamed human liver.

Methods: Different single-cell RNA sequencing methods were combined with in silico analyses on intrahepatic and peripheral T cells from patients with PSC (n = 11) and healthy donors (HDs, n = 4).

Monocytes as Potential Mediators of Pathogen-Induced T-Helper 17 Differentiation in Patients With Primary Sclerosing Cholangitis (PSC).

Background And Aims: T cells from patients with primary sclerosing cholangitis (PSC) show a prominent interleukin (IL)-17 response upon stimulation with bacteria or fungi, yet the reasons for this dominant T-helper 17 (Th17) response in PSC are not clear. Here, we analyzed the potential role of monocytes in microbial recognition and in skewing the T-cell response toward Th17.

Approach And Results: Monocytes and T cells from blood and livers of PSC patients and controls were analyzed ex vivo and in vitro using transwell experiments with cholangiocytes.