Tissue-Resident NK Cells: Development, Maturation, and Clinical Relevance

Hashemi, Elaheh; Malarkannan, Subramaniam

doi:10.3390/cancers12061553

Cited by 76 publications

(90 citation statements)

References 241 publications

(327 reference statements)

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“…Natural killer (NK) cells are effector cells of the innate immune system with crucial functions in infection and tumor surveillance [ 86 , 87 ]. NK cells express CD56 and are classified as CD56 bright NK cells in tissues with the ability to release cytokines, whereas CD56 dim NK cells are preferentially found in blood and are characterized by their direct killing capacity [ 88 , 89 ]. NK cells were shown to have an important role in regulating liver fibrosis by directly killing activated hepatic stellate cells via the receptors NKG2D and NKp46 and the p38/PI3K/AKT pathway [ 90 , 91 , 92 ].…”

Section: The Role Of Inflammation In Nafldmentioning

confidence: 99%

Inflammatory Mechanisms Underlying Nonalcoholic Steatohepatitis and the Transition to Hepatocellular Carcinoma

Peiseler

Tacke

2021

Cancers

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Nonalcoholic fatty liver disease (NAFLD) is a rising chronic liver disease and comprises a spectrum from simple steatosis to nonalcoholic steatohepatitis (NASH) to end-stage cirrhosis and risk of hepatocellular carcinoma (HCC). The pathogenesis of NAFLD is multifactorial, but inflammation is considered the key element of disease progression. The liver harbors an abundance of resident immune cells, that in concert with recruited immune cells, orchestrate steatohepatitis. While inflammatory processes drive fibrosis and disease progression in NASH, fueling the ground for HCC development, immunity also exerts antitumor activities. Furthermore, immunotherapy is a promising new treatment of HCC, warranting a more detailed understanding of inflammatory mechanisms underlying the progression of NASH and transition to HCC. Novel methodologies such as single-cell sequencing, genetic fate mapping, and intravital microscopy have unraveled complex mechanisms behind immune-mediated liver injury. In this review, we highlight some of the emerging paradigms, including macrophage heterogeneity, contributions of nonclassical immune cells, the role of the adaptive immune system, interorgan crosstalk with adipose tissue and gut microbiota. Furthermore, we summarize recent advances in preclinical and clinical studies aimed at modulating the inflammatory cascade and discuss how these novel therapeutic avenues may help in preventing or combating NAFLD-associated HCC.

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Section: The Role Of Inflammation In Nafldmentioning

confidence: 99%

Inflammatory Mechanisms Underlying Nonalcoholic Steatohepatitis and the Transition to Hepatocellular Carcinoma

Peiseler

Tacke

2021

Cancers

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“…CD56 bright NK cells have the capacity to produce large quantities of cytokines, while CD56 dim NK cells are more cytotoxic and express more killer immunoglobulin (Ig)‐like receptors (KIR) as well as Fc‐ϒ receptor III (Fc‐GR III, CD16) [36–38]. NK cells express activating and inhibitory receptors on their surface, which define their functional properties [34,35,39,40]. NK cells lyse target cells that express insufficient or lack MHC‐1 molecules, whereas cells that express MHC‐I molecule are not affected.…”

Section: The Biology Of Nk Cellsmentioning

confidence: 99%

Immunological basis of early clearance ofMycobacterium tuberculosisinfection: the role of natural killer cells

Abebe

2021

Clinical and Experimental Immunology

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Summary Tuberculosis (TB) kills more people than any other single infectious disease globally. Despite decades of research, there is no vaccine to prevent TB transmission. Bacille Calmette–Guérin (BCG) vaccine, developed a century ago, is effective against childhood (disseminated and miliary) TB. However, its protective efficacy against pulmonary TB varies from 0 to 80% in different populations. One of the main reasons for the lack of an effective vaccine against TB is the lack of complete understanding about correlates of protective immunity on which to base vaccine design and development. However, some household contacts who are extensively exposed to Mtb infection remain persistently negative to tuberculin skin test and interferon‐gamma assay. These individuals, called ‘resisters’, clear Mtb infection early before the development of acquired immunity. The immunological basis of early Mtb clearance is yet to be established; however, innate lymphocytes such as monocytes/macrophages, dendritic cells, neutrophils and natural killer cells, and innate‐like T cells such as mucosal‐associated invariant T cells, invariant natural killer (NK) T cells and gamma‐delta (γδ) T cells, have been implicated in this early protection. In recent years, NK cells have attracted increasing attention because of their role in controlling Mtb infection. Emerging data from animal and epidemiological studies indicate that NK cells play a significant role in the fight against Mtb. NK cells express various surface markers to recognize and kill both Mtb and Mtb‐infected cells. This review presents recent advances in our understanding of NK cells in the fight against Mtb early during infection, with emphasis on cohort studies.

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“…Recent research on tissueresident NK cells (trNK) has provided new knowledge on this cell population. Unlike their counterparts that circulate in peripheral blood (cNK), trNK differ in the profile of MHC-recognizing receptors and cytokines produced [18] . Hepatic trNKs maintain hepatic homeostasis by reacting to liver insults such as acute viral infection and hepatoma, the latter of which elicits a clonal-like expansion of trNKs that enable a memory-like, more robust immune response [19] .…”

Section: Natural Killer (Nk) Cellsmentioning

confidence: 99%