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Differential Expression of microRNAs in Thymic Epithelial Cells from Trypanosoma cruzi Acutely Infected Mice: Putative Role in Thymic Atrophy.

Linhares-Lacerda L, Palu CC, Ribeiro-Alves M, Paredes BD, Morrot A, Garcia-Silva MR, Cayota A, Savino W - Front Immunol (2015)

Bottom Line: Thymic epithelial cells (TEC) play a major role in the intrathymic T cell differentiation.In silico analysis revealed that these miRNAs may control target mRNAs known to be responsible for chemotaxis, cell adhesion, and cell death.Considering that we sorted TEC in the initial phase of thymocyte loss, it is conceivable that changes in TEC miRNA expression profile are functionally related to thymic atrophy, providing new clues to better understanding the mechanisms of the thymic involution seen in experimental Chagas disease.

View Article: PubMed Central - PubMed

Affiliation: Laboratory on Thymus Research, Institute Oswaldo Cruz, Oswaldo Cruz Foundation , Rio de Janeiro , Brazil.

ABSTRACT
A common feature seen in acute infections is a severe atrophy of the thymus. This occurs in the murine model of acute Chagas disease. Moreover, in thymuses from Trypanosoma cruzi acutely infected mice, thymocytes exhibit an increase in the density of fibronectin and laminin integrin-type receptors, with an increase in migratory response ex vivo. Thymic epithelial cells (TEC) play a major role in the intrathymic T cell differentiation. To date, the consequences of molecular changes promoted by parasite infection upon thymus have not been elucidated. Considering the importance of microRNA for gene expression regulation, 85 microRNAs (mRNAs) were analyzed in TEC from T. cruzi acutely infected mice. The infection significantly modulated 29 miRNAs and modulation of 9 was also dependent whether TEC sorted out from the thymus exhibited cortical or medullary phenotype. In silico analysis revealed that these miRNAs may control target mRNAs known to be responsible for chemotaxis, cell adhesion, and cell death. Considering that we sorted TEC in the initial phase of thymocyte loss, it is conceivable that changes in TEC miRNA expression profile are functionally related to thymic atrophy, providing new clues to better understanding the mechanisms of the thymic involution seen in experimental Chagas disease.

No MeSH data available.


Related in: MedlinePlus

miRNA relative expression in thymic epithelial cells from control and infected mice. The miRNA expression of 85 miRNAs was analyzed for each sorted TEC population, in five replicates, with samples from control (dark blue) and infected (light blue) mice being paired. We present the 29 miRNAs that were significant (adjusted p-value ≤0.05) differentially expressed due to infection and the samples clustered according to expression profile similarity. Three groups of samples were identified based on their expression profile, as illustrated by the dendrogram.
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Figure 3: miRNA relative expression in thymic epithelial cells from control and infected mice. The miRNA expression of 85 miRNAs was analyzed for each sorted TEC population, in five replicates, with samples from control (dark blue) and infected (light blue) mice being paired. We present the 29 miRNAs that were significant (adjusted p-value ≤0.05) differentially expressed due to infection and the samples clustered according to expression profile similarity. Three groups of samples were identified based on their expression profile, as illustrated by the dendrogram.

Mentions: We analyzed herein 85 miRNAs in order to approach putative molecular alterations in TEC following response to T. cruzi acute infection, and that might be related to the previously reported thymic atrophy and abnormal scape of immature thymocyte (20, 21, 32, 33). We found that 29 out of the 85 miRNAs were significantly differently expressed between TEC from infected and normal mice (adjusted p ≤ 0.05), all were up-regulated (Figure 3) whereas differences in further 13 miRNAs were suggestive (Figure S3 in Supplementary Material).


Differential Expression of microRNAs in Thymic Epithelial Cells from Trypanosoma cruzi Acutely Infected Mice: Putative Role in Thymic Atrophy.

Linhares-Lacerda L, Palu CC, Ribeiro-Alves M, Paredes BD, Morrot A, Garcia-Silva MR, Cayota A, Savino W - Front Immunol (2015)

miRNA relative expression in thymic epithelial cells from control and infected mice. The miRNA expression of 85 miRNAs was analyzed for each sorted TEC population, in five replicates, with samples from control (dark blue) and infected (light blue) mice being paired. We present the 29 miRNAs that were significant (adjusted p-value ≤0.05) differentially expressed due to infection and the samples clustered according to expression profile similarity. Three groups of samples were identified based on their expression profile, as illustrated by the dendrogram.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543887&req=5

Figure 3: miRNA relative expression in thymic epithelial cells from control and infected mice. The miRNA expression of 85 miRNAs was analyzed for each sorted TEC population, in five replicates, with samples from control (dark blue) and infected (light blue) mice being paired. We present the 29 miRNAs that were significant (adjusted p-value ≤0.05) differentially expressed due to infection and the samples clustered according to expression profile similarity. Three groups of samples were identified based on their expression profile, as illustrated by the dendrogram.
Mentions: We analyzed herein 85 miRNAs in order to approach putative molecular alterations in TEC following response to T. cruzi acute infection, and that might be related to the previously reported thymic atrophy and abnormal scape of immature thymocyte (20, 21, 32, 33). We found that 29 out of the 85 miRNAs were significantly differently expressed between TEC from infected and normal mice (adjusted p ≤ 0.05), all were up-regulated (Figure 3) whereas differences in further 13 miRNAs were suggestive (Figure S3 in Supplementary Material).

Bottom Line: Thymic epithelial cells (TEC) play a major role in the intrathymic T cell differentiation.In silico analysis revealed that these miRNAs may control target mRNAs known to be responsible for chemotaxis, cell adhesion, and cell death.Considering that we sorted TEC in the initial phase of thymocyte loss, it is conceivable that changes in TEC miRNA expression profile are functionally related to thymic atrophy, providing new clues to better understanding the mechanisms of the thymic involution seen in experimental Chagas disease.

View Article: PubMed Central - PubMed

Affiliation: Laboratory on Thymus Research, Institute Oswaldo Cruz, Oswaldo Cruz Foundation , Rio de Janeiro , Brazil.

ABSTRACT
A common feature seen in acute infections is a severe atrophy of the thymus. This occurs in the murine model of acute Chagas disease. Moreover, in thymuses from Trypanosoma cruzi acutely infected mice, thymocytes exhibit an increase in the density of fibronectin and laminin integrin-type receptors, with an increase in migratory response ex vivo. Thymic epithelial cells (TEC) play a major role in the intrathymic T cell differentiation. To date, the consequences of molecular changes promoted by parasite infection upon thymus have not been elucidated. Considering the importance of microRNA for gene expression regulation, 85 microRNAs (mRNAs) were analyzed in TEC from T. cruzi acutely infected mice. The infection significantly modulated 29 miRNAs and modulation of 9 was also dependent whether TEC sorted out from the thymus exhibited cortical or medullary phenotype. In silico analysis revealed that these miRNAs may control target mRNAs known to be responsible for chemotaxis, cell adhesion, and cell death. Considering that we sorted TEC in the initial phase of thymocyte loss, it is conceivable that changes in TEC miRNA expression profile are functionally related to thymic atrophy, providing new clues to better understanding the mechanisms of the thymic involution seen in experimental Chagas disease.

No MeSH data available.


Related in: MedlinePlus