Kupffer Cells Promote the Differentiation of Adult Liver Hematopoietic Stem and Progenitor Cells into Lymphocytes via ICAM-1 and LFA-1 Interaction

Abstract

It has been reported that the adult liver contains hematopoietic stem and progenitor cells (HSPCs), which are associated with long-term hematopoietic reconstitution activity. Hepatic hematopoiesis plays an important role in the generation of cells involved in liver diseases. However, how the progenitors differentiate into functional myeloid cells and lymphocytes in the liver microenvironment remains unknown. In the present study, HSPC transplantation experiments were used to confirm that adult murine liver HSPCs differentiate into both myeloid cells and lymphocytes (preferentially T cells) compared with bone marrow HSPCs. Using a coculture system comprised of kupffer cells and HSPCs, we found that kupffer cells promote adult liver HSPCs to primarily generate T cells and B cells. We then demonstrated that kupffer cells can also promote HSPC expansion. A blockade of intercellular cell adhesion molecule-1 (ICAM-1) in a liver HSPC and kupffer cell coculture system impaired the adhesion, expansion, and differentiation of HSPCs. These results suggest a critical role of kupffer cells in the maintenance and promotion of adult mouse liver hematopoiesis. These findings provide important insight into understanding liver extramedullary hematopoiesis and its significance, particularly under the state of some liver diseases, such as hepatitis, nonalcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC).

Single-cell analysis reveals the origins and intrahepatic development of liver-resident IFN-γ-producing γδ T cells

“… 32 Similar to the thymus and small intestine, the liver microenvironment supports hematopoiesis and lymphocyte differentiation by secreting hematopoiesis-promoting cytokines, such as IL-7 and SCF. 12 , 38 Whether liver-specific LSM cells can differentiate into intrahepatic γδ T cells in situ remains unknown. In the present study, based on the scRNA-seq analysis, we found that γδ T precursor cells (C3-T/L) exist not only in the thymus but also in the liver.…”

“… 11 Adult liver HSPCs have also been reported to differentiate into T and B lymphocytes. 12 More recent studies have focused on the developmental origins of γδ T cells and related transcriptional programs. 13 , 14 However, the precise developmental program, particularly the origins and extrathymic developmental pathways associated with liver γδ T cells, remains largely unsolved.…”

β2 Integrins—Multi-Functional Leukocyte Receptors in Health and Disease

“…These alterations may be caused by a lack of CD11d/CD18 expression in the thymus resulting in inaccurate T cell development. The overall importance of β2 integrins for the expansion of HPSC (hematopoietic stem and progenitor cells) was demonstrated in a study by Meng and co-workers [80]. In a coculture system of HSPCs and Kupffer cells, that constitute the liver-resident macrophage population [81], Kuppfer cells promoted HSPC expansion and differentiation to lymphocytes.…”

Bioinformatic Analysis of Crosstalk Between circRNA, miRNA, and Target Gene Network in NAFLD

“…Some of these genes could directly affect NAFLD development, and the others may influence NAFLD by some related effects. The level of ICAM1 was markedly enhanced after the stimulation of lipopolysaccharide in the liver, and the blockade of it may destroy the cells’ adhesion and expansion ( Meng et al, 2019 ). CD44 , is proved to be of great significance in non-alcoholic steatohepatitis.…”