Related Experiment Video

Updated: Jul 6, 2026

Development of Stem Cell-derived Antigen-specific Regulatory T Cells Against Autoimmunity
10:10

Development of Stem Cell-derived Antigen-specific Regulatory T Cells Against Autoimmunity

Published on: November 8, 2016

The proapoptotic and antimitogenic protein p66SHC acts as a negative regulator of lymphocyte activation and

Francesca Finetti1, Michela Pellegrini, Cristina Ulivieri

  • 1Department of Evolutionary Biology, University of Siena, Siena, Italy.

Blood
|March 13, 2008
PubMed

Insights

Mice lacking p66Shc protein develop a lupus-like autoimmune disease due to uncontrolled lymphocyte activation. This study reveals p66Shc as a key regulator of immune tolerance, crucial for preventing autoimmunity.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • The ShcA locus produces three protein isoforms, including p66Shc, which regulates T-cell receptor (TCR) signaling and apoptosis.
  • p66Shc plays a role in T-cell activation and programmed cell death.

Purpose of the Study:

  • To investigate the effects of p66Shc deficiency on lymphocyte development and immune homeostasis.
  • To determine the role of p66Shc in regulating immune tolerance and preventing autoimmune diseases.

Main Methods:

  • Studied p66Shc knockout (p66Shc(-/-)) mice to assess lymphocyte development and autoimmune phenotypes.
  • Analyzed lymphocyte activation, proliferation, autoantibody production, and immune complex deposition in p66Shc(-/-) mice.
  • Evaluated immune responses in p66Shc(-/-) mice following vaccination and allergen sensitization.

Main Results:

  • p66Shc(-/-) mice spontaneously develop an age-related lupus-like autoimmune disease.
  • Characterized by peripheral T- and B-cell activation, autoantibody production, and immune complex deposition leading to glomerulonephritis and alopecia.
  • p66Shc(-/-) lymphocytes exhibit enhanced proliferation upon antigen receptor engagement and stronger immune responses in vivo.

Conclusions:

  • p66Shc acts as a negative regulator of lymphocyte activation.
  • Loss of p66Shc function leads to the breakdown of immunologic tolerance.
  • p66Shc deficiency results in the development of systemic autoimmunity.

More Related Videos

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells10:26

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells

Published on: January 20, 2019

Study of Dendritic Cell Development by Short Hairpin RNA-Mediated Gene Knockdown in a Hematopoietic Stem and Progenitor Cell Line In vitro06:12

Study of Dendritic Cell Development by Short Hairpin RNA-Mediated Gene Knockdown in a Hematopoietic Stem and Progenitor Cell Line In vitro

Published on: March 7, 2022

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...