Impaired natural killer cell subset phenotypes in human obesity

Bähr, Ina; Jahn, Janine; Zipprich, Alexander; Pahlow, Inge; Spielmann, Julia; Kielstein, Heike

doi:10.1007/s12026-018-8989-4

Cited by 67 publications

(75 citation statements)

References 60 publications

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“…In accordance to the results in mice and rats, obesity was shown to be associated with a decreased NK cell number in blood, liver, uterine, or colon tissue in humans (74,99,(146)(147)(148)(149), whereas several other studies did not observe any differences in the NK cell number comparing normal-weight and obese humans (71,72,84,(150)(151)(152)(153)(154)(155) (Table 4). These discrepancies may be caused by the use of different markers and methods to identify NK cells and subsets in blood and different tissues and individual parameters in the study population, like gender, BMI, ethnicity, and nutritional or metabolic variances.…”

Section: Effects Of Systemic Obesity On Human Nk Cellssupporting

confidence: 84%

“…Whereas, several studies did not find any differences on the CD56 dim /CD56 bright ratio comparing NK cells isolated from normal-weight and obese humans (72,150,152,156), results of two studies revealed evidence for a decrease of CD56 dim CD16 bright NK cells and an increase of CD56 bright CD16 dim/neg NK cells in obesity (71,147). As previous studies observed that the CD56 dim CD16 bright NK cell subset can convert into the CD56 bright CD16 dim subset under the influence of specific cytokines and hormones, it had been assumed that obesity-related metabolites induce a conversion of CD56 dim CD16 bright in CD56 bright CD16 dim/neg NK cells in obese individuals (71,(162)(163)(164). Analyses of the subset-specific NK cell phenotype also demonstrated a decrease in NKG2Dpositive and CD69-positive CD56 dim CD16 bright NK cells (71).…”

Section: Effects Of Systemic Obesity On Human Nk Cellsmentioning

confidence: 80%

“…Investigations demonstrated that the leptin receptor (obesity receptor, ObR) is expressed on splenic and peripheral blood NK cells of rats as well as on human hepatic and peripheral blood NK cells (67-76) ( Table 1). Although leptin receptor expression levels on NK cells are rather dim, functional data upon leptin treatment performed by different laboratories demonstrate a functional role for this receptor on NK cells (69)(70)(71)(72)(73)77).…”

Section: Studies On Leptinmentioning

confidence: 99%

“…As previous studies observed that the CD56 dim CD16 bright NK cell subset can convert into the CD56 bright CD16 dim subset under the influence of specific cytokines and hormones, it had been assumed that obesity-related metabolites induce a conversion of CD56 dim CD16 bright in CD56 bright CD16 dim/neg NK cells in obese individuals (71,(162)(163)(164). Analyses of the subset-specific NK cell phenotype also demonstrated a decrease in NKG2Dpositive and CD69-positive CD56 dim CD16 bright NK cells (71). In addition, data on NK cell cytokine production demonstrated a decreased expression of IFN-γ-positive CD56 dim CD16 bright NK cells in obese subjects, indicating an downregulation of the immunoregulatory effect of this NK cell subset in obesity (71).…”

Section: Effects Of Systemic Obesity On Human Nk Cellsmentioning

confidence: 99%

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Obesity-Associated Alterations of Natural Killer Cells and Immunosurveillance of Cancer

et al. 2020

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Obesity is accompanied by a systemic chronic low-grade inflammation as well as dysfunctions of several innate and adaptive immune cells. Recent findings emphasize an impaired functionality and phenotype of natural killer (NK) cells under obese conditions. This review provides a detailed overview on research related to overweight and obesity with a particular focus on NK cells. We discuss obesity-associated alterations in subsets, distribution, phenotype, cytotoxicity, cytokine secretion, and signaling cascades of NK cells investigated in vitro as well as in animal and human studies. In addition, we provide recent insights into the effects of physical activity and obesity-associated nutritional factors as well as the reduction of body weight and fat mass on NK cell functions of obese individuals. Finally, we highlight the impact of impaired NK cell physiology on obesity-associated diseases, focusing on the elevated susceptibility for viral infections and increased risk for cancer development and impaired treatment response.NK cells are large granular lymphocytes that mediate rapid innate immunity against viruses, bacteria, parasites, and tumor cells without prior sensitization. NK cells primarily develop and mature in the bone marrow, migrate through the bloodstream, and seed into secondary lymphoid organs, like thymus, spleen, and lymph nodes as well as in other peripheral tissues, like lung, liver, kidney, uterus, and the gastrointestinal tract (23). In blood, NK cells represent 1-6% of all leukocytes and comprise up to 15% of human peripheral blood mononuclear cells (PBMCs). Human NK cells have been defined by the expression of adhesion molecule CD56 and by the absence of the T cell marker CD3. Based on their expression level of CD56 and the Fcγ receptor CD16, NK cells are subdivided into different subpopulations. The two major and classically defined subsets are the CD56 dim CD16 bright NK cells and the CD56 bright CD16 dim/neg NK cells. CD56 dim CD16 bright NK cells represent about 90% of all NK cells and are predominantly found in peripheral blood (24). They are mostly responsible for cytotoxic activity and target cell killing but are also a source of pro-inflammatory Abbreviations: ACM, adipocyte-conditioned media; Adamts3, a disintegrin-like and metallopeptidase with thrombospondin type 1 motif, 3; AdipoR, adiponectin receptor; Anxa8, annexin A8; AT, adipose tissue; Bax, Bcl-2-associated X protein; Bcl, B-cell lymphoma; BMI, body mass index; CCR, CC chemokine receptor; Csf1r, colony stimulating factor 1 receptor; CX3CR1, C-X3-C-motif chemokine receptor 1; DNAM-1, DNAX accessory molecule-1; ESR, estrogen receptor; FasL, Fas ligand; IFN-γ, interferon; GM-CSF; granulocyte macrophage colony-stimulating factor; H6pd, hexose-6-phosphate dehydrogenase; Hk2, hexokinase 2; IL, interleukinIL-6R; interleukin-6 receptor; Il18rap, interleukin 18 receptor accessory protein; IP-10, interferon gamma-induced protein 10; JAK, Janus kinase; KIR, killer immunoglobulin-like receptor; Klra1, killer lectin-like receptor subfamil...

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Section: Effects Of Systemic Obesity On Human Nk Cellssupporting

confidence: 84%

Section: Effects Of Systemic Obesity On Human Nk Cellsmentioning

confidence: 80%

Section: Studies On Leptinmentioning

confidence: 99%

Section: Effects Of Systemic Obesity On Human Nk Cellsmentioning

confidence: 99%

See 2 more Smart Citations

Obesity-Associated Alterations of Natural Killer Cells and Immunosurveillance of Cancer

et al. 2020

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“…Impairing of the NK cell function is one of the common factors behind these links. For example, obesity has been known to impair NK cell function and then lead to an increased risk for severe infections and several cancer types ( 48, 49 ), while chronic family stress is consistently associated with decreases in NK cell cytotoxicity ( 50 ). These results indicated that NK function impaired by either genetic defects or regulatory factors such as depression, obesity and diabetes could increase cancer incidence.…”

Section: Resultsmentioning

confidence: 99%

Inherited defects in natural killer cells shape tumor immune microenvironment, clinical outcome and immunotherapy response

Xu¹,

Zou

et al. 2018

Preprint

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27Tumor immune microenvironment (TIME) plays an important role in metastasis and 28 immunotherapy. However, it has been not much known how to classify TIMEs and how TIMEs are 29 genetically regulated. Here we showed that tumors were classified into TIME-rich, -intermediate and -30 poor subtypes which had significant differences in clinical outcomes, abundances of tumor-infiltrating 31 lymphocytes (TILs), degree of key immune programs' activation, and immunotherapy response across 32 13 common cancer types (n= ~6,000). Furthermore, TIME-intermediate/-poor patients had significantly 33 more inherited genetic defects (i.e., functional germline variants) in natural killer (NK) cells, antigen 34 processing and presentation (APP) and Wnt signaling pathways than TIME-rich patients, and so did 35 cancer patients than non-cancer individuals (n=4,500). These results suggested that individuals who 36 had more inherited defects in NK cells, APP and Wnt pathways had higher risk of developing 37 cancers. Moreover, in the 13 common cancers the number of inheritably defected genes of NK 38 cells was significantly negative-correlated with patients' survival, TILs' abundance in TIMEs and 39 immunotherapy response, suggesting that inherited defects in NK cells alone were sufficient to shape 40 TILs' recruitment, clinical outcome and immunotherapy response, highlighting that NK cell activation 41 was required in the 13 cancer types to drive the recruitment of immune troops into TIMEs. Thus, we 42proposed that cancer was a disease of NK cell inherited deficiencies. These results had implications in 43 identifying of high-risk individuals based on germline genomes, implementing precision cancer 44 prevention by adoptive transfer of healthy NK cells, and improving existing immunotherapies by 45 combining of adoptive NK cell transfer (i.e., converting TIME-intermediate/-poor tumors into TIME-46 rich tumors) in and anti-PD-1 or CAR-T therapy. 47 48 49

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Factors Associated With Complete Remission After Rituximab Therapy for Pemphigus

et al. 2019

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IMPORTANCE Rituximab has emerged as a front-line therapy for pemphigus, but prognostic factors for achieving complete remission off therapy (CROT) with oral systemic agents remain unknown. OBJECTIVES To describe rates of CROT and relapse and identify prognostic factors for achieving CROT after rituximab therapy for pemphigus. DESIGN, SETTING, AND PARTICIPANTS A single-center, retrospective, cohort study was conducted at the University of Pennsylvania including 112 patients with pemphigus treated with rituximab with at least 12 months' clinical follow-up after the start of rituximab therapy. Multivariate regression analysis of factors predictive of CROT and Kaplan-Meier analysis of disease relapse were conducted. The study included patients treated with rituximab from

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Impaired natural killer cell subset phenotypes in human obesity

Cited by 67 publications

References 60 publications

Obesity-Associated Alterations of Natural Killer Cells and Immunosurveillance of Cancer

Obesity-Associated Alterations of Natural Killer Cells and Immunosurveillance of Cancer

Inherited defects in natural killer cells shape tumor immune microenvironment, clinical outcome and immunotherapy response

Factors Associated With Complete Remission After Rituximab Therapy for Pemphigus

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