bims-nastce 2021-11-28 papers

Issue of 2021‒11‒28
five papers selected by
Petra Hirsova
Mayo Clinic College of Medicine

Int J Mol Sci. 2021 Nov 11. pii: 12190. [Epub ahead of print]22(22):

T Cell Subsets and Natural Killer Cells in the Pathogenesis of Nonalcoholic Fatty Liver Disease.

Yoseph Asmelash Gebru, Haripriya Gupta, Hyeong Seop Kim, Jung A Eom, Goo Hyun Kwon, Eunju Park, Jin-Ju Jeong, Sung-Min Won, Satya Priya Sharma, Raja Ganesan, Dong Joon Kim, Ki Tae Suk.

Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by hepatic accumulation of excess lipids. T cells are commonly classified into various subsets based on their surface markers including T cell receptors, type of antigen presentation and pathophysiological functions. Several studies have implicated various T cell subsets and natural killer (NK) cells in the progression of NAFLD. While NK cells are mainly components of the innate hepatic immune system, the majority of T cell subsets can be part of both the adaptive and innate systems. Several studies have reported that various stages of NAFLD are accompanied by the accumulation of distinct T cell subsets and NK cells with different functions and phenotypes observed usually resulting in proinflammatory effects. More importantly, the overall stimulation of the intrahepatic T cell subsets is directly influenced by the homeostasis of the gut microbiota. Similarly, NK cells have been found to accumulate in the liver in response to pathogens and tumors. In this review, we discussed the nature and pathophysiological roles of T cell subsets including γδ T cells, NKT cells, Mucosal-associated invariant T (MAIT) cells as well as NK cells in NAFLD.

Keywords: MHC I; MHC II; NK cells; T cells; antigen presenting cell; gut microbiota; nonalcoholic fatty liver disease

DOI: https://doi.org/10.3390/ijms222212190

Biochem J. 2021 Nov 26. 478(22): 3999-4004

Regulation of Tim-3 function by binding to phosphatidylserine.

Lawrence P Kane.

Tim-3 is a transmembrane protein that is highly expressed on subsets of chronically stimulated CD4+ helper and CD8+ cytotoxic T cells, with more transient expression during acute activation and infection. Tim-3 is also constitutively expressed by multiple types of myeloid cells. Like other TIM family members, Tim-3 can bind to phosphatidylserine displayed by apoptotic cells, and this interaction has been shown to mediate uptake of such cells by dendritic cells and cross-presentation of antigens to CD8+ T cells. In contrast, how the recognition of PS by Tim-3 might regulate the function of Tim-3+ T cells is not known. In their recent paper, Lemmon and colleagues demonstrate for the first time that recognition of PS by Tim-3 leads to enhanced T cell activation.

DOI: https://doi.org/10.1042/BCJ20210652

Mediators Inflamm. 2021 ;2021 8481013

Role and Function of T Cell-Derived Exosomes and Their Therapeutic Value.

Yuanyuan Shao, Xiaofeng Pan, Rong Fu.

Exosomes are membrane-bound extracellular vesicles that are produced in the endosomal compartment of most eukaryotic cells. Containing proteins, RNA, and DNA, exosomes mediate intercellular communication between different cell types by transferring their contents and thus are involved in numerous physiological and pathological processes. T cells are an indispensable part of adaptive immunity, and the functions of T cell-derived exosomes have been widely studied. In the more than three decades since the discovery of exosomes, several studies have revealed that T cell-derived exosomes play a novel role in cell-to-cell signaling, especially in inflammatory responses, autoimmunity, and infectious diseases. In this review, we will summarize the function of T cell-derived exosomes and their therapeutic potential.

DOI: https://doi.org/10.1155/2021/8481013

Nat Rev Immunol. 2021 Nov 23.

Immune ageing at single-cell resolution.

Denis A Mogilenko, Irina Shchukina, Maxim N Artyomov.

Ageing leads to profound alterations in the immune system and increases susceptibility to some chronic, infectious and autoimmune diseases. In recent years, widespread application of single-cell techniques has enabled substantial progress in our understanding of the ageing immune system. These comprehensive approaches have expanded and detailed the current views of ageing and immunity. Here we review a body of recent studies that explored how the immune system ages using unbiased profiling techniques at single-cell resolution. Specifically, we discuss an emergent understanding of age-related alterations in innate and adaptive immune cell populations, antigen receptor repertoires and immune cell-supporting microenvironments of the peripheral tissues. Focusing on the results obtained in mice and humans, we describe the multidimensional data that align with established concepts of immune ageing as well as novel insights emerging from these studies. We further discuss outstanding questions in the field and highlight techniques that will advance our understanding of immune ageing in the future.

DOI: https://doi.org/10.1038/s41577-021-00646-4

iScience. 2021 Nov 19. 24(11): 103337

Stabilin receptors clear LPS and control systemic inflammation.

Fatima Cabral, Mustafa Al-Rahem, John Skaggs, Thushara A Thomas, Naresh Kumar, Qian Wu, Paolo Fadda, Lianbo Yu, John M Robinson, Jonghan Kim, Ekta Pandey, Xinghui Sun, Wael N Jarjour, Murugesan V S Rajaram, Edward N Harris, Latha P Ganesan.

Lipopolysaccharides (LPSs) cause lethal endotoxemia if not rapidly cleared from blood circulation. Liver sinusoidal endothelial cells (LSEC) systemically clear LPS by unknown mechanisms. We discovered that LPS clearance through LSEC involves endocytosis and lysosomal inactivation via Stabilin-1 and 2 (Stab1 and Stab2) but does not involve TLR4. Cytokine production was inversely related to clearance/endocytosis of LPS by LSEC. When exposed to LPS, Stabilin double knockout mice (Stab DK) and Stab1 KO, but not Stab2 KO, showed significantly enhanced systemic inflammatory cytokine production and early death compared with WT mice. Stab1 KO is not significantly different from Stab DK in circulatory LPS clearance, LPS uptake and endocytosis by LSEC, and cytokine production. These data indicate that (1) Stab1 receptor primarily facilitates the proactive clearance of LPS and limits TLR4-mediated inflammation and (2) TLR4 and Stab1 are functionally opposing LPS receptors. These findings suggest that endotoxemia can be controlled by optimizing LPS clearance by Stab1.

Keywords: Biological sciences; Immune response; Molecular biology

DOI: https://doi.org/10.1016/j.isci.2021.103337