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Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver diseases that span simple steatosis, metabolic dysfunctionassociated steatohepatitis (MASH) and fibrosis and may progress to cirrhosis and cancer. The pathogenesis of MASLD is multifactorial and is driven by environmental, genetic, metabolic and immune factors. This review will focus on the role of the type 3 cytokines IL-17 and IL-22 in MASLD pathogenesis and progression. IL-17 and IL-22 are produced by similar adaptive and innate immune cells such as Th17 and innate lymphoid cells, respectively. IL-17-related signaling is upregulated during MASLD resulting in increased chemokines and proinflammatory cytokines in the liver microenvironment, enhanced recruitment of myeloid cells and T cells leading to exacerbation of inflammation and liver disease progression. IL-17 may also act directly by activating hepatic stellate cells resulting in increased fibrosis. In contrast, IL-22 is a pleiotropic cytokine with a dominantly protective signature in MASLD and is currently being tested as a therapeutic strategy. IL-22 also exhibits beneficial metabolic effects and abrogates MASH-related inflammation and fibrosis development via inducing the production of anti-oxidants and anti-apoptotic factors. A sex-dependent effect has been attributed to both cytokines, most importantly to IL-22 in MASLD or related conditions. Altogether, IL-17 and IL-22 are key effectors in MASLD pathogenesis and progression. We will review the role of these two cytokines and cells that produce them in the development of MASLD, their interaction with host factors driving MASLD including sexual dimorphism, and their potential therapeutic benefits. [ABSTRACT FROM AUTHOR]

The interaction between vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) plays an important role in the modulation of vascular tone. There is, however, no information on whether direct physical communication regulates the intracellular calcium levels of human VECs (hVECs) and (or) human VSMCs (hVSMCs). Thus, the objective of the study is to verify whether co-culture of hVECs and hVSMCs modulates cytosolic ([[[Ca.sup.2+]].sub.c]) and nuclear calcium ([[[Ca.sup.2+]].sub.n]) levels via physical contact and (or) factors released by both cell types. Quantitative 3D confocal microscopy for [[[[Ca.sup.2+]].sub.c] and [[[[Ca.sup.2+]].sub.n] measurement was performed in cultured hVECs or hVSMCs or in co-culture of hVECs-hVSMCs. Our results show that: (1) physical contact between hVECs-hVECs or hVSMCs-hVSMCs does not affect [[[[Ca.sup.2+]].sub.c] and [[[[Ca.sup.2+]].sub.n] in these 2 cell types; (2) physical contact between hVECs and hVSMCs induces a significant increase only of [[[[Ca.sup.2+]].sub.n] of hVECs without affecting the level of [[[[Ca.sup.2+]].sub.c] and [[[Ca.sup.2+]].sub.n] of hVSMCs; and (3) preconditioned culture medium of hVECs or hVSMCs does not affect [[[[Ca.sup.2+]].sub.c] and [[[[Ca.sup.2+]].sub.n] of both types of cells. We concluded that physical contact between hVECs and hVSMCs only modulates [[[[Ca.sup.2+]].sub.n] in hVECs. The increase of [[[[Ca.sup.2+]].sub.n] in hVECs may modulate nuclear functions that are calcium dependent. Key words: vascular endothelial cells, vascular smooth muscle cells, co-culture, nuclear calcium, calcium release. L'interaction entre les cellules endotheliales vasculaires (CEV) et les cellules musculaires lisses vasculaires (CMLV) joue un role important dans la modulation du tonus vasculaire. Il n'existe cependant aucune information quant aux effets de leur communication physique directe sur la regulation des concentrations intracellulaires de calcium dans les CEV humaines (CEVh) ou les CMLV humaines (CMLVh). Par consequent, l'etude avait pour but de verifier si la co-culture de CEVh avec des CMLVh entraine une modulation des concentrations de calcium cytosolique ([[[[Ca.sup.2+]].sub.c]) et nucleaire ([[[[Ca.sup.2+]].sub.n]) par l'intermediaire d'un contact physique et (ou) de facteurs liberes par les deux types de cellules. A l'aide de la microscopie confocale quantitative en 3D, nous avons mesure les [[[[Ca.sup.2+]].sub.c] et les [[[[Ca.sup.2+]].sub.n] dans les CEVh et les CMLVh en culture ou en co-culture les unes avec les autres (CEVh-CMLVh). Nos resultats montrent les choses suivantes: (1) Le contact physique entre CEVh-CEVh ou CMLVh-CMLVh n'a pas d'effet sur les [[[[Ca.sup.2+]].sub.c] ni sur les [[[[Ca.sup.2+]].sub.n] dans ces deux types cellulaires; (2) Le contact physique entre CEVh-CMLVh entraine une augmentation marquee uniquement des [[[[Ca.sup.2+]].sub.n] dans les CEVh, sans affecter les [[[[Ca.sup.2+]].sub.c] ni les [[[[Ca.sup.2+]].sub.n] dans les CMLVh; et (3) Le milieu de culture preconditionne des CEVh ou des CMLVh n'a aucun effet sur les [[[[Ca.sup.2+]].sub.c] ni les [[[[Ca.sup.2+]].sub.n] pour les deux types de cellules. Nous en sommes arrives a la conclusion que le contact physique entre les CEVh et les CMLVh entraine une modulation uniquement des [[[[Ca.sup.2+]].sub.n] dans les CEVh. Cette augmentation des [[[[Ca.sup.2+]].sub.n] dans les CEVh pourrait entrainer une modulation de fonctions nucleaires qui dependent du calcium. [Traduit par la Redaction] Mots-cles: cellules endotheliales vasculaires, cellules musculaires lisses vasculaires, co-culture, calcium nucleaire, liberation de calcium., Introduction Physical contact between the same type of cells involves different types of junctions such as tight junctions (Alberts 1994), adherence junctions (Alberts 1994), platelet-endothelial cell adhesion molecule (DeLisser et [...]

Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinctspatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury. [ABSTRACT FROM AUTHOR]