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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Comprehensive Survey of miRNA-mRNA Interactions Reveals That Ccr7 and Cd247 (CD3 zeta) are Posttranscriptionally Controlled in Pancreas Infiltrating T Lymphocytes of Non-Obese Diabetic (NOD) Mice

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Autor(es):
Fornari, Thais A. [1] ; Donate, Paula B. [1] ; Assis, Amanda F. [1] ; Macedo, Claudia [1] ; Sakamoto-Hojo, Elza T. [1, 2] ; Donadi, Eduardo A. [1, 3] ; Passos, Geraldo A. [4, 5, 1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Mol Immunogenet Grp, BR-14049900 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Dept Biol, Fac Philosophy Sci & Letters Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med, Div Clin Immunol, BR-14049900 Ribeirao Preto, SP - Brazil
[4] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Morphol Physiol & Basic Pathol, Discipline Genet, BR-14040904 Ribeirao Preto, SP - Brazil
[5] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Morphol Physiol & Basic Pathol, Discipline Mol Biol, BR-14040904 Ribeirao Preto, SP - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: PLoS One; v. 10, n. 11 NOV 25 2015.
Citações Web of Science: 12
Resumo

In autoimmune type 1 diabetes mellitus (T1D), auto-reactive clones of CD4(+) and CD8(+) T lymphocytes in the periphery evolve into pancreas-infiltrating T lymphocytes (PILs), which destroy insulin-producing beta-cells through inflammatory insulitis. Previously, we demonstrated that, during the development of T1D in non-obese diabetic (NOD) mice, a set of immune/inflammatory reactivity genes were differentially expressed in T lymphocytes. However, the posttranscriptional control involving miRNA interactions that occur during the evolution of thymocytes into PILs remains unknown. In this study, we postulated that miRNAs are differentially expressed during this period and that these miRNAs can interact with mRNAs involved in auto-reactivity during the progression of insulitis. To test this hypothesis, we used NOD mice to perform, for the first time, a comprehensive survey of miRNA and mRNA expression as thymocytes mature into peripheral CD3(+) T lymphocytes and, subsequently, into PILs. Reconstruction of miRNA-mRNA interaction networks for target prediction revealed the participation of a large set of miRNAs that regulate mRNA targets related to apoptosis, cell adhesion, cellular regulation, cellular component organization, cellular processes, development and the immune system, among others. The interactions between miR-202-3p and the Ccr7 chemokine receptor mRNA or Cd247 (Cd3 zeta chain) mRNA found in PILs are highlighted because these interactions can contribute to a better understanding of how the lack of immune homeostasis and the emergence of autoimmunity (e.g., T1D) can be associated with the decreased activity of Ccr7 or Cd247, as previously observed in NOD mice. We demonstrate that these mRNAs are controlled at the posttranscriptional level in PILs. (AU)

Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
Beneficiário:Fernando de Queiroz Cunha
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 08/56594-8 - Controle do transcriptoma no diabetes mellitus
Beneficiário:Geraldo Aleixo da Silva Passos Júnior
Linha de fomento: Auxílio à Pesquisa - Temático