The impact of body mass index on adaptive immune cells in the human bone marrow

Abstract Background. Obesity has been associated with chronic inflammation and oxidative stress. Both conditions play a determinant role in the pathogenesis of age-related diseases, such as immunosenescence. Adipose tissue can modulate the function of the immune system with the secretion of molecules influencing the phenotype of immune cells. Recently, the importance of the bone marrow (BM) in the maintenance of antigen-experienced adaptive immune cells has been documented. Despite this, whether high body mass index (BMI) may affect immune cells in the BM and the production of molecules supporting the maintenance of these cells it is unknown. Methods. Using flow cytometry, the frequency and the phenotype of immune cell populations were measured in paired BM and PB samples obtained from persons with different BMI. Furthermore, the expression of BM cytokines was assessed. The influence of cytomegalovirus (CMV) on T cell subsets was additionally considered, dividing the donors into the CMV - and CMV + groups. Results. Our study suggests that increased BMI may affect both the maintenance and the phenotype of adaptive immune cells in the BM. While the BM levels of IL-15 and IL-6, supporting the survival of highly differentiated T cells, and oxygen radicals increased in overweight persons, the production of IFNγ and TNF by CD8 + T cells was reduced. In addition, the frequency of B cells and CD4 + T cells positively correlated with BMI in the BM of CMV - persons. Finally, the frequency of several T cell subsets, and the expression of senescence/exhaustion markers within these subpopulations, were affected by BMI. In particular, the levels of bona fide memory T cells may be reduced in overweight persons. Conclusion. Our work suggests that obesity may represent an independent risk factor supporting immunosenescence, in addition to aging and CMV. Metabolic interventions may help in improving the fitness of the immune system in the elderly.

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The impact of body mass index on adaptive immune cells in the human bone marrow

10.21203/rs.2.22852/v2 ◽

2020 ◽

Author(s):

Luca Pangrazzi ◽

Erin Naismith ◽

Carina Miggitsch ◽

Jose’ Antonio Carmona Arana ◽

Michael Keller ◽

...

Keyword(s):

Body Mass Index ◽

Bone Marrow ◽

T Cells ◽

Immune System ◽

T Cell ◽

Immune Cells ◽

Memory T Cells ◽

T Cell Subsets ◽

Adaptive Immune ◽

Adaptive Immune Cells

Abstract Background. Obesity has been associated with chronic inflammation and oxidative stress. Both conditions play a determinant role in the pathogenesis of age-related diseases, such as immunosenescence. Adipose tissue can modulate the function of the immune system with the secretion of molecules influencing the phenotype of immune cells. The importance of the bone marrow (BM) in the maintenance of antigen-experienced adaptive immune cells has been documented in mice. Recently, some groups have investigated the survival of effector/memory T cells in the human BM. Despite this, whether high body mass index (BMI) may affect immune cells in the BM and the production of molecules supporting the maintenance of these cells it is unknown.Methods. Using flow cytometry, the frequency and the phenotype of immune cell populations were measured in paired BM and PB samples obtained from persons with different BMI. Furthermore, the expression of BM cytokines was assessed. The influence of cytomegalovirus (CMV) on T cell subsets was additionally considered, dividing the donors into the CMV- and CMV+ groups.Results. Our study suggests that increased BMI may affect both the maintenance and the phenotype of adaptive immune cells in the BM. While the BM levels of IL-15 and IL-6, supporting the survival of highly differentiated T cells, and oxygen radicals increased in overweight persons, the production of IFNγ and TNF by CD8+ T cells was reduced. In addition, the frequency of B cells and CD4+ T cells positively correlated with BMI in the BM of CMV- persons. Finally, the frequency of several T cell subsets, and the expression of senescence/exhaustion markers within these subpopulations, were affected by BMI. In particular, the levels of bona fide memory T cells may be reduced in overweight persons.Conclusion. Our work suggests that, in addition to aging and CMV, obesity may represent an additional risk factor for immunosenescence in adaptive immune cells. Metabolic interventions may help in improving the fitness of the immune system in the elderly.

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The impact of body mass index on adaptive immune cells in the human bone marrow

10.21203/rs.2.22852/v3 ◽

2020 ◽

Author(s):

Luca Pangrazzi ◽

Erin Naismith ◽

Carina Miggitsch ◽

Jose’ Antonio Carmona Arana ◽

Michael Keller ◽

...

Keyword(s):

Body Mass Index ◽

Bone Marrow ◽

T Cells ◽

Immune System ◽

T Cell ◽

Immune Cells ◽

Memory T Cells ◽

T Cell Subsets ◽

Adaptive Immune ◽

Adaptive Immune Cells

Abstract Background. Obesity has been associated with chronic inflammation and oxidative stress. Both conditions play a determinant role in the pathogenesis of age-related diseases, such as immunosenescence. Adipose tissue can modulate the function of the immune system with the secretion of molecules influencing the phenotype of immune cells. The importance of the bone marrow (BM) in the maintenance of antigen-experienced adaptive immune cells has been documented in mice. Recently, some groups have investigated the survival of effector/memory T cells in the human BM. Despite this, whether high body mass index (BMI) may affect immune cells in the BM and the production of molecules supporting the maintenance of these cells it is unknown.Methods. Using flow cytometry, the frequency and the phenotype of immune cell populations were measured in paired BM and PB samples obtained from persons with different BMI. Furthermore, the expression of BM cytokines was assessed. The influence of cytomegalovirus (CMV) on T cell subsets was additionally considered, dividing the donors into the CMV- and CMV+ groups.Results. Our study suggests that increased BMI may affect both the maintenance and the phenotype of adaptive immune cells in the BM. While the BM levels of IL-15 and IL-6, supporting the survival of highly differentiated T cells, and oxygen radicals increased in overweight persons, the production of IFNγ and TNF by CD8+ T cells was reduced. In addition, the frequency of B cells and CD4+ T cells positively correlated with BMI in the BM of CMV- persons. Finally, the frequency of several T cell subsets, and the expression of senescence/exhaustion markers within these subpopulations, were affected by BMI. In particular, the levels of bona fide memory T cells may be reduced in overweight persons.Conclusion. Our work suggests that, in addition to aging and CMV, obesity may represent an additional risk factor for immunosenescence in adaptive immune cells. Metabolic interventions may help in improving the fitness of the immune system in the elderly.

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The impact of aging on memory T cell phenotype and function in the human bone marrow

Journal of Leukocyte Biology ◽

10.1189/jlb.0611299 ◽

2011 ◽

Vol 91 (2) ◽

pp. 197-205 ◽

Cited By ~ 54

Author(s):

Dietmar Herndler-Brandstetter ◽

Katja Landgraf ◽

Alexandar Tzankov ◽

Brigitte Jenewein ◽

Regina Brunauer ◽

...

Keyword(s):

Bone Marrow ◽

T Cell ◽

Human Bone ◽

Human Bone Marrow ◽

Cell Phenotype ◽

Memory T Cell ◽

And Function ◽

The Impact

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The Role of Innate and Adaptive Immune Cells in the Pathogenesis and Development of the Inflammatory Response in Ulcerative Colitis

Journal of Clinical Medicine ◽

10.3390/jcm11020400 ◽

2022 ◽

Vol 11 (2) ◽

pp. 400

Author(s):

Aleksandra Kałużna ◽

Paweł Olczyk ◽

Katarzyna Komosińska-Vassev

Keyword(s):

Ulcerative Colitis ◽

Immune Response ◽

Immune Cells ◽

Chronic Inflammatory Disease ◽

Lymphoid Cells ◽

Cytotoxic Lymphocytes ◽

Adaptive Immune ◽

Adaptive Immune Cells ◽

Th17 Lymphocytes ◽

The Impact

Ulcerative colitis (UC) is a chronic inflammatory disease with an underlying excessive immune response directed against resident microbiota and/or dietary antigens. Both innate and adaptive immune cells play a crucial role in the pathogenesis of UC. In the case of innate immune response cells, neutrophils, dendritic cells, macrophages have a crucial impact on the development of the disease, as well as innate lymphoid cells, which have received a particular attention in recent years. On the other hand, mechanisms of the adaptive immune response involve cells such as: cytotoxic lymphocytes, regulatory lymphocytes Treg, or helper lymphocytes Th–Th2, Th9, Th17, Th22, among which significant discoveries about Th9 and Th17 lymphocytes have been made in recent years. Due to the presence of antibodies directed against resident microbiota or one’s own tissues, the influence of B lymphocytes on the development of UC is also highlighted. Additionally, the impact of cytokines on shaping the immune response as well as sustaining inflammation seems to be crucial. This review briefly describes the current state of knowledge about the involvement of the innate and adaptive immune systems in the pathogenesis of UC. The review is based on personal selection of literature that were retrieved by a selective search in PubMed using the terms “ulcerative colitis” and “pathogenesis of ulcerative colitis”. It included systematic reviews, meta-analyses and clinical trials. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents.

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CD34+ isolation from human bone marrow v1

10.17504/protocols.io.bvswn6fe ◽

2021 ◽

Author(s):

Mohsen Khosravi-Maharlooei ◽

Markus Holzl ◽

Austin Chen ◽

Megan Sykes

Keyword(s):

Bone Marrow ◽

Immune Cells ◽

Mixed Lymphocyte Reaction ◽

Human Bone ◽

Human Bone Marrow ◽

Humanized Mice ◽

Cd34 Cells ◽

Bone Marrow Ablation ◽

Marrow Ablation

This protocol details the steps for isolating CD34+ cells from human bone marrow. The CD34+ cells isolated from this protocol can be used for generating humanized mice through reconstitution of immune cells via IV injection after bone marrow ablation. These cells can also be used for mixed lymphocyte reaction experiments.

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The impact of aging on lymphocytes and their function in the human bone marrow

Experimental Gerontology ◽

10.1016/j.exger.2015.01.025 ◽

2015 ◽

Vol 68 ◽

pp. 99-100

Author(s):

T. Pritz ◽

Julian Lair ◽

Michael Ban ◽

R. Rauf ◽

M. Krismer ◽

...

Keyword(s):

Bone Marrow ◽

Human Bone ◽

Human Bone Marrow ◽

The Impact

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The impact of body mass index on the risk of early progression of smoldering multiple myeloma to symptomatic myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.8032 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 8032-8032

Author(s):

Wilson I. Gonsalves ◽

S. Vincent Rajkumar ◽

Angela Dispenzieri ◽

Martha Lacy ◽

Francis Buadi ◽

...

Keyword(s):

Body Mass Index ◽

Multiple Myeloma ◽

Bone Marrow ◽

Body Mass ◽

Plasma Cells ◽

Progression Rate ◽

Early Progression ◽

Bone Marrow Plasma ◽

The Impact

8032 Background: Human adipocytes can contribute directly to the in vitro growth and progression of multiple myeloma (MM) cell lines. Clinically, an elevated body mass index (BMI) has been associated with an increased risk of MGUS and a shorter time to progression (TTP) of MGUS to MM. However, the impact of BMI on the risk of early progression to MM from a more advanced plasma cell disorder such as smoldering MM (SMM) remains unknown. Methods: This study included patients (pts) with a known or new diagnosis of SMM evaluated at the Mayo Clinic, Rochester from January 2000-December 2010. Pts were classified based on their BMI as: normal (< 25) and elevated (>/= 25) BMI. Progression to symptomatic MM was defined by the development of hypercalcemia, renal insufficiency, anemia or lytic bone lesions. Results: There were 306 pts with a diagnosis of SMM who were included in this analysis. The median follow up was 106 months. There were 203 (66%) pts who progressed to symptomatic MM at last follow up. The median BMI of the group was 27.5 (Range: 17.2 – 56.4). There were 228 (75%) pts with an elevated BMI. There were 76 (28%) pts who had myeloma defining events (MDEs) such as a serum free light chain ratio > 100 or > 60% clonal bone marrow plasma cells at initial evaluation. MDEs were present in 17% and 33% of pts with a normal and elevated BMI respectively (P = 0.011). The median TTP of SMM to MM in pts with a normal and elevated BMI was 64 and 36 months respectively (P = 0.0006). The 2-year progression rate of SMM to symptomatic MM in pts with a normal and elevated BMI was 16% and 42% respectively (P < 0.0001). Upon limiting the analysis to only SMM pts without MDEs at initial evaluation (N =187), the 2-year progression rate to symptomatic MM with a normal and elevated BMI was 15% and 33% respectively (P = 0.013). In a multivariable model, only elevated BMI (P = 0.004) and increasing clonal bone marrow plasma cells (P = 0.001) was statistically significant in predicting for a 2-year progression to MM. Conclusions: SMM pts with an elevated BMI appear to have a higher risk of early progression to MM than those with a normal BMI. This study provides evidence of a potentially modifiable risk factor for the progression of SMM to MM and warrants confirmation in larger studies.

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