Homeostasis of IL-15 dependent lymphocyte subsets in the liver

Cepero-Donates, Yuneivy; Rakotoarivelo, Volatiana; Mayhue, Marian; Ma, Averil; Chen, Yi-Guang; Ramanathan, Sheela

doi:10.1016/j.cyto.2015.12.012

Cited by 20 publications

(17 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-2Rα forms part of the IL-2 as well as the IL-15 receptor (in complex with IL-15Rα) (42). IL-15 is important for NK cell survival, activation and function (43,44), is strongly expressed in the liver (45)(46)(47), and hepatocyte-and KC-derived IL-15/IL-15Rα directly regulates the homeostasis of liver NK cells via trans-presentation (48). Conversely IL12RB, which encodes IL-12Rβ, is upregulated on cNK cells and induces IFN-γ production when stimulated by IL-12, highlighting that cNK and lrNK cells are regulated by different cytokines in the liver microenvironment (49).…”

Section: Activating the Lrnk Cell Immune Responsementioning

confidence: 99%

Insights Into Human Intrahepatic NK Cell Function From Single Cell RNA Sequencing Datasets

Jameson

Robinson

2021

Front. Immunol.

View full text Add to dashboard Cite

Diverse populations of natural killer (NK) cells have been identified in circulating peripheral blood and a wide variety of different tissues and organs. These tissue-resident NK cell populations are phenotypically distinct from circulating NK cells, however, functional descriptions of their roles within tissues are lacking. Recent advances in single cell RNA sequencing (scRNA-seq) have enabled detailed transcriptional profiling of tissues at the level of single cells and provide the opportunity to explore NK cell diversity within tissues. This review explores potential novel functions of human liver-resident (lr)NK cells identified in human liver scRNA-seq studies. By comparing these datasets we identified up-regulated and down-regulated genes associated with lrNK cells clusters. These genes encode a number of activating and inhibiting receptors, as well as signal transduction molecules, which highlight potential unique pathways that lrNK cells utilize to respond to stimuli within the human liver. This unique receptor repertoire of lrNK cells may confer the ability to regulate a number of immune cell populations, such as circulating monocytes and T cells, while avoiding activation by liver hepatocytes and Kupffer cells. Validating the expression of these receptors on lrNK cells and the proposed cellular interactions within the human liver will expand our understanding of the liver-specific homeostatic roles of this tissue-resident immune cell population.

show abstract

Section: Activating the Lrnk Cell Immune Responsementioning

confidence: 99%

Insights Into Human Intrahepatic NK Cell Function From Single Cell RNA Sequencing Datasets

Jameson

Robinson

2021

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Tissue specific ablation of IL-15Ra has revealed specific, but distinct patterns of requirement for the source of the transpresented IL-15 (18,19). We have shown IL-15 transpresentation by hepatocytes and macrophages is required for the maintenance of NK and NKT cells in the liver (20).…”

Section: Introductionmentioning

confidence: 73%

“…Hematopoietic and Non-Hematopoietic IL-15 Contribute to the Control of L. monocytogenes IL-15 from hematopoietic and non-hematopoietic cells are required for efficient activation of IL-15 dependent immune cells (7,19,20,48). To determine the relative contribution of IL-15 from the hematopoietic and non-hematopoietic compartments, we generated radiation chimeras and infected them with low dose L. monocytogenes two months after lethal radiation and hematopoietic reconstitution.…”

Section: Exogenous Ifng Partially Controls L Monocytogenes Infection In Il15-/-micementioning

confidence: 99%

IL-15Rα-Independent IL-15 Signaling in Non-NK Cell-Derived IFNγ Driven Control of Listeria monocytogenes

et al. 2021

Self Cite

View full text Add to dashboard Cite

Interleukin-15, produced by hematopoietic and parenchymal cells, maintains immune cell homeostasis and facilitates activation of lymphoid and myeloid cell subsets. IL-15 interacts with the ligand-binding receptor chain IL-15Rα during biosynthesis, and the IL-15:IL-15Rα complex is trans-presented to responder cells that express the IL-2/15Rβγc complex to initiate signaling. IL-15-deficient and IL-15Rα-deficient mice display similar alterations in immune cell subsets. Thus, the trimeric IL-15Rαβγc complex is considered the functional IL-15 receptor. However, studies on the pathogenic role of IL-15 in inflammatory and autoimmune diseases indicate that IL-15 can signal independently of IL-15Rα via the IL-15Rβγc dimer. Here, we compared the ability of mice lacking IL-15 (no signaling) or IL-15Rα (partial/distinct signaling) to control Listeria monocytogenes infection. We show that IL-15-deficient mice succumb to infection whereas IL-15Rα-deficient mice clear the pathogen as efficiently as wildtype mice. IL-15-deficient macrophages did not show any defect in bacterial uptake or iNOS expression in vitro. In vivo, IL-15 deficiency impaired the accumulation of inflammatory monocytes in infected spleens without affecting chemokine and pro-inflammatory cytokine production. The inability of IL-15-deficient mice to clear L. monocytogenes results from impaired early IFNγ production, which was not affected in IL-15Rα-deficient mice. Administration of IFNγ partially enabled IL-15-deficient mice to control the infection. Bone marrow chimeras revealed that IL-15 needed for early bacterial control can originate from both hematopoietic and non-hematopoietic cells. Overall, our findings indicate that IL-15-dependent IL-15Rα-independent signaling via the IL-15Rβγc dimeric complex is necessary and sufficient for the induction of IFNγ from sources other than NK/NKT cells to control bacterial pathogens.

show abstract

“…Orthotopic liver transplantation experiments using IRF-1 knockout mice revealed that hepatocytes are major producers of soluble IL-15 and IL-15Rα complexes among liver cell populations [ 97 ]. A study using IL-15 knockout mice and IL-15Rα conditional knockout mice showed that hepatocyte-mediated IL-15 signaling by IL-15Rα expression is required to maintain the homeostasis of NK and NKT cells in the liver [ 98 ]. In turn, activated NK and NKT cells produce inflammatory cytokines such as IL-6, TNF, and IFN-γ.…”

Section: Liver-resident Natural Killer Cellsmentioning

confidence: 99%

Crosstalk between Metabolic Disorders and Immune Cells

Saitoh

Wijk

Nakajima

2021

IJMS

View full text Add to dashboard Cite

Metabolic syndrome results from multiple risk factors that arise from insulin resistance induced by abnormal fat deposition. Chronic inflammation owing to obesity primarily results from the recruitment of pro-inflammatory M1 macrophages into the adipose tissue stroma, as the adipocytes within become hypertrophied. During obesity-induced inflammation in adipose tissue, pro-inflammatory cytokines are produced by macrophages and recruit further pro-inflammatory immune cells into the adipose tissue to boost the immune response. Here, we provide an overview of the biology of macrophages in adipose tissue and the relationship between other immune cells, such as CD4+ T cells, natural killer cells, and innate lymphoid cells, and obesity and type 2 diabetes. Finally, we discuss the link between the human pathology and immune response and metabolism and further highlight potential therapeutic targets for the treatment of metabolic disorders.

show abstract

Homeostasis of IL-15 dependent lymphocyte subsets in the liver

Cited by 20 publications

References 42 publications

Insights Into Human Intrahepatic NK Cell Function From Single Cell RNA Sequencing Datasets

Insights Into Human Intrahepatic NK Cell Function From Single Cell RNA Sequencing Datasets

IL-15Rα-Independent IL-15 Signaling in Non-NK Cell-Derived IFNγ Driven Control of Listeria monocytogenes

Crosstalk between Metabolic Disorders and Immune Cells

Contact Info

Product

Resources

About