Dataset Information

Talin Plays a Critical Role in the Maintenance of the Regulatory T Cell Pool.

ABSTRACT: Talin, a cytoskeletal protein essential in mediating integrin activation, has been previously shown to be involved in the regulation of T cell proliferation and function. In this study, we describe a role for talin in maintaining the homeostasis and survival of the regulatory T (Treg) cell pool. T cell-specific deletion of talin in Tln1fl/flCd4Cre mice resulted in spontaneous lymphocyte activation, primarily due to numerical and functional deficiencies of Treg cells in the periphery. Peripheral talin-deficient Treg cells were unable to maintain high expression of IL-2R?, resulting in impaired IL-2 signaling and ultimately leading to increased apoptosis through downregulation of prosurvival proteins Bcl-2 and Mcl-1. The requirement for talin in maintaining high IL-2R? expression by Treg cells was due, in part, to integrin LFA-1-mediated interactions between Treg cells and dendritic cells. Collectively, our data suggest a critical role for talin in Treg cell-mediated maintenance of immune homeostasis.

SUBMITTER: Klann JE

PROVIDER: S-EPMC5507362 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Talin Plays a Critical Role in the Maintenance of the Regulatory T Cell Pool.

Klann Jane E JE Remedios Kelly A KA Kim Stephanie H SH Metz Patrick J PJ Lopez Justine J Mack Lauren A LA Zheng Ye Y Ginsberg Mark H MH Petrich Brian G BG Chang John T JT

Journal of immunology (Baltimore, Md. : 1950) 20170517 12

Talin, a cytoskeletal protein essential in mediating integrin activation, has been previously shown to be involved in the regulation of T cell proliferation and function. In this study, we describe a role for talin in maintaining the homeostasis and survival of the regulatory T (Treg) cell pool. T cell-specific deletion of talin in Tln1fl/flCd4Cre mice resulted in spontaneous lymphocyte activation, primarily due to numerical and functional deficiencies of Treg ...[more]

PMID: 28515282

Similar Datasets

Project description:BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a devastating disease with a median survival of only three to 5?years. Fibroblast proliferation is a hallmark of IPF as is secretion of extracellular matrix proteins from fibroblasts. However, it is still uncertain how IPF fibroblasts acquire the ability to progressively proliferate. Periostin is a matricellular protein highly expressed in the lung tissues of IPF patients, playing a critical role in the pathogenesis of pulmonary fibrosis. However, it remains undetermined whether periostin affects lung fibroblast proliferation. METHODS:In this study, we first aimed at identifying periostin-dependently expressed genes in lung fibroblasts using DNA microarrays. We then examined whether expression of cyclins and CDKs controlling cell cycle progression occur in a periostin-dependent manner. We next examined whether downregulation of cell proliferation-promoting genes by knockdown of periostin or integrin, a periostin receptor, using siRNA, is reflected in the cell proliferation of lung fibroblasts. We then looked at whether lung fibroblasts derived from IPF patients also require periostin for maximum proliferation. We finally investigated whether CP4715, a potent inhibitor against integrin ?V?3 (a periostin receptor), which we have recently found blocks TGF-? signaling, followed by reduced BLM-induced pulmonary fibrosis in mice, can block proliferation of lung fibroblasts derived from IPF patients. RESULTS:Many cell-cycle-related genes are involved in the upregulated or downregulated genes by periostin knockdown. We confirmed that in lung fibroblasts, periostin silencing downregulates expression of several cell-cycle-related molecules, including the cyclin, CDK, and, E2F families, as well as transcription factors such as B-MYB and FOXM1. Periostin or integrin silencing slowed proliferation of lung fibroblasts and periostin silencing increased the distribution of the G0/G1 phase, whereas the distribution of the G2/M phase was decreased. Lung fibroblasts derived from IPF patients also required periostin for maximum proliferation. Moreover, CP4715 downregulated proliferation along with expression of cell-cycle-related genes in IPF lung fibroblasts as well as in normal lung fibroblasts. CONCLUSIONS:Periostin plays a critical role in the proliferation of lung fibroblasts and the present results provide us a solid basis for considering inhibitors of the periostin/integrin ?V?3 interaction for the treatment of IPF patients.

Dataset Information

Talin Plays a Critical Role in the Maintenance of the Regulatory T Cell Pool.

Publications

Talin Plays a Critical Role in the Maintenance of the Regulatory T Cell Pool.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets