Thymic extracellular matrix in human malnutrition

Lyra, Jurandy S. P. Ocampo; Madi, Kalil; Maeda, Cristina T.; Savino, Wilson

doi:10.1002/path.1711710312

Cited by 36 publications

(41 citation statements)

References 23 publications

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“…Thus, protein-energy malnutrition-related thymocyte depletion results from enhanced thymocyte death plus decreased thymocyte proliferation. It should be pointed out that the major change in the thymic lymphoid compartment is also observed in human subjects suffering from malnutrition: a severe thymic atrophy with cortical thymocyte depletion is a consistent finding in necropsies of malnourished subjects (1,10) . Indeed, by means of echography, atrophy of the organ was also observed in vivo in malnourished children, as compared to age-matched healthy individuals (11) .…”

Section: Thymocyte Development Is Altered In Protein-energy Malnutritionmentioning

confidence: 70%

Nutritional imbalances and infections affect the thymus: consequences on T-cell-mediated immune responses

Savino

Dardenne

2010

Proc. Nutr. Soc.

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The thymus gland, where T lymphocyte development occurs, is targeted in malnutrition secondary to protein energy deficiency. There is a severe thymic atrophy, resulting from massive thymocyte apoptosis (particularly affecting the immature CD4 + CD8 + cell subset) and decrease in cell proliferation. The thymic microenvironment (the non-lymphoid compartment that drives intrathymic T-cell development) is also affected in malnutrition: morphological changes in thymic epithelial cells were found, together with a decrease of thymic hormone production, as well as an increase of intrathymic contents of extracellular proteins. Profound changes in the thymus can also be seen in deficiencies of vitamins and trace elements. Taking Zn deficiency as an example, there is a substantial thymic atrophy. Importantly, marginal Zn deficiency in AIDS subjects, children with diarrhoea and elderly persons, significantly impairs the host's immunity, resulting in an increased risk of opportunistic infections and mortality; effects that are reversed by Zn supplementation. Thymic changes also occur in acute infectious diseases, including a severe thymic atrophy, mainly due to the depletion of CD4 + CD8 + thymocytes, decrease in thymocyte proliferation, in parallel to densification of the epithelial network and increase in the extracellular matrix contents, with consequent disturbances in thymocyte migration and export. In conclusion, the thymus is targeted in several conditions of malnutrition as well as in acute infections. These changes are related to the impaired peripheral immune response seen in malnourished and infected individuals. Thus, strategies inducing thymus replenishment should be considered as adjuvant therapeutics to improve immunity in malnutrition and/or acute infectious diseases.

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Section: Thymocyte Development Is Altered In Protein-energy Malnutritionmentioning

confidence: 70%

Nutritional imbalances and infections affect the thymus: consequences on T-cell-mediated immune responses

Savino

Dardenne

2010

Proc. Nutr. Soc.

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“…It is important to highlight that the major change in the thymic lymphoid compartment is also observed in humans suffering from malnutrition: a severe thymic atrophy with cortical thymocyte depletion is a consistent finding in necropsies of malnourished subjects (Chandra, 1992;Lyra et al, 1993). Indeed, by means of echography, atrophy of the organ was also observed in vivo in malnourished children (Parent et al, 1994).…”

Section: Phenotypic and Functional Changes Of Thymocytes In Malnutritionmentioning

confidence: 79%

“…This abnormally dense ECM network contained fibronectin, laminin and type IV collagen. Importantly, the enhancement of thymic ECM in malnourished individuals positively correlated with the degree of thymocyte depletion (Lyra et al, 1993). This correlation may represent a cause -effect relationship in which the contact of thymocytes with abnormally high amounts of thymic ECM triggers and=or enhances programmed cell death.…”

Section: Increased Extracellular Matrix In the Thymus Of Malnourishedmentioning

confidence: 87%

The thymus gland is a target in malnutrition

2002

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Malnutrition, secondary to deficiency in uptake of proteins, metal elements or vitamins, consistently results in changes in the thymus gland. The organ undergoes a severe atrophy due to apoptosis-induced thymocyte depletion, particularly affecting the immature CD4 þ CD8 þ cells, as well as a decrease in cell proliferation. Such a feature is apparently linked to a hormonal imbalance, involving decrease of leptin and consequent raise of glucocorticoid hormone levels in the serum. Interestingly, this picture can be reversed after appropriate diet rehabilitation. The thymic microenvironment is also affected in malnutrition: morphological changes in thymic epithelial cells were found, together with a decrease of thymic hormone production by these cells. Additionally, intrathymic contents of extracellular proteins, such as fibronectin, laminin and collagens, are increased in the thymuses from malnourished children. Conjointly, the bulk of data discussed herein clearly points to the notion that the thymus gland is a target in malnutrition. Nevertheless, further relevant information regarding the physiology of the thymus, including the cytokine=chemokine secretion as well as the positive and negative selection events driven by TCR=MHC-peptide interactions in malnutrition, remains to be defined. These are questions that need to be answered in order to have a better understanding of the immunodeficiency seen in malnourished individuals.

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“…Few studies exist that explore the relationship between malnutrition and the ECM. Lyra et al (31) observed an increase in ECM density within the thymus in malnourished children, which was considered to be responsible for the depletion of thymocytes. Reif et al (32) found a decrease in ECM components within the liver.…”

Section: Discussionmentioning

confidence: 99%

Protein-energy malnutrition halts hemopoietic progenitor cells in the G0/G1 cell cycle stage, thereby altering cell production rates

Borelli

Barros

Nakajima

et al. 2009

Braz J Med Biol Res

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Protein energy malnutrition (PEM) is a syndrome that often results in immunodeficiency coupled with pancytopenia. Hemopoietic tissue requires a high nutrient supply and the proliferation, differentiation and maturation of cells occur in a constant and balanced manner, sensitive to the demands of specific cell lineages and dependent on the stem cell population. In the present study, we evaluated the effect of PEM on some aspects of hemopoiesis, analyzing the cell cycle of bone marrow cells and the percentage of progenitor cells in the bone marrow. Two-month-old male Swiss mice (N = 7-9 per group) were submitted to PEM with a low-protein diet (4%) or were fed a control diet (20% protein) ad libitum. When the experimental group had lost about 20% of their original body weight after 14 days, we collected blood and bone marrow cells to determine the percentage of progenitor cells and the number of cells in each phase of the cell cycle. Animals of both groups were stimulated with 5-fluorouracil. Blood analysis, bone marrow cell composition and cell cycle evaluation was performed after 10 days. Malnourished animals presented anemia, reticulocytopenia and leukopenia. Their bone marrow was hypocellular and depleted of progenitor cells. Malnourished animals also presented more cells than normal in phases G0 and G1 of the cell cycle. Thus, we conclude that PEM leads to the depletion of progenitor hemopoietic populations and changes in cellular development. We suggest that these changes are some of the primary causes of pancytopenia in cases of PEM.

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Thymic extracellular matrix in human malnutrition

Cited by 36 publications

References 23 publications

Nutritional imbalances and infections affect the thymus: consequences on T-cell-mediated immune responses

Nutritional imbalances and infections affect the thymus: consequences on T-cell-mediated immune responses

The thymus gland is a target in malnutrition

Protein-energy malnutrition halts hemopoietic progenitor cells in the G0/G1 cell cycle stage, thereby altering cell production rates

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