Small interference ITGA6 gene targeting in the human thymic epithelium differentially regulates the expression of immunological synapse-related genes

Thumbnail Image
File version

Version of Record (VoR)

Golbert, Daiane Cristina F
Santana-Van-Vliet, Eliane
Ribeiro-Alves, Marcelo
da Fonseca, Marbella Maria B
Lepletier, Ailin
Mendes-da-Cruz, Daniella Areas
Loss, Guilherme
Cotta-de-Almeida, Vinicius
Vasconcelos, Ana Tereza R
Savino, Wilson
Griffith University Author(s)
Primary Supervisor
Other Supervisors
File type(s)

The thymus supports differentiation of T cell precursors. This process requires relocation of developing thymocytes throughout multiple microenvironments of the organ, mainly with thymic epithelial cells (TEC), which control intrathymic T cell differentiation influencing the formation and maintenance of the immunological synapse. In addition to the proteins of the major histocompatibility complex (MHC), this structure is supported by several adhesion molecules. During the process of thymopoiesis, we previously showed that laminin-mediated interactions are involved in the entrance of T-cell precursors into the thymus, as well as migration of differentiating thymocytes within the organ. Using small interference RNA strategy, we knocked-down the ITGA6 gene (which encodes the CD49f integrin α-chain) in cultured human TEC, generating a decrease in the expression of the corresponding CD49f subunit, in addition to modulation in several other genes related to cell adhesion and migration. Thymocyte adhesion to TEC was significantly impaired, comprising both immature and mature thymocyte subsets. Moreover, we found a modulation of the MHC, with a decrease in membrane expression of HLA-ABC, in contrast with increase in the expression of HLA-DR. Interestingly, the knockdown of the B2M gene (encoding the β-2 microglobulin of the HLA-ABC complex) increased CD49f expression levels, thus unraveling the existence of a cross-talk event in the reciprocal control of CD49f and HLA-ABC. Our data suggest that the expression levels of CD49f may be relevant in the general control of MHC expression by TEC and consequently the corresponding synapse with developing thymocytes mediated by the T-cell receptor.

Journal Title

Cell Adhesion & Migration

Conference Title
Book Title




Thesis Type
Degree Program
Publisher link
Patent number
Grant identifier(s)
Rights Statement
Rights Statement

© The Author(s) 2018. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported (CC BY-NC 3.0) License, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.

Item Access Status
Access the data
Related item(s)

Biochemistry and cell biology

Other biological sciences

Science & Technology

Life Sciences & Biomedicine

Cell Biology

extracellular matrix


Persistent link to this record

Golbert, DCF; Santana-Van-Vliet, E; Ribeiro-Alves, M; da Fonseca, MMB; Lepletier, A; Mendes-da-Cruz, DA; Loss, G; Cotta-de-Almeida, V; Vasconcelos, ATR; Savino, W, Small interference ITGA6 gene targeting in the human thymic epithelium differentially regulates the expression of immunological synapse-related genes, Cell Adhesion & Migration, 2018, 12 (2), pp. 152-167