Related Experiment Video
Updated: Jun 3, 2026
12:59
Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 26, 2013
Trp53 negatively regulates autoimmunity via the STAT3-Th17 axis
Shuzhong Zhang1, Mingquan Zheng, Ryoko Kibe
1Gene Therapy Program, Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, 533 Bolivar St., New Orleans, LA 70112, USA.
Summary
The tumor suppressor p53 controls T helper 17 (Th17) cells, suppressing autoimmunity. Loss of p53 in T cells enhances Th17 responses and leads to autoimmune disease, suggesting p53 is a key regulator of immune homeostasis.
Area of Science:
- Immunology
- Molecular Biology
- Autoimmunity
Background:
- The tumor suppressor p53 regulates physiological processes and inhibits inflammation.
- p53's role in autoimmune effector T cells remains largely unexplored.
Purpose of the Study:
- To investigate the function of p53 in T cells regarding autoimmunity.
- To elucidate the molecular mechanisms by which p53 influences T cell responses.
Main Methods:
- Generated p53-deficient mice (p53(null)CD45.1) by genetic crossing.
- Assessed autoimmune pathology, Th17 cell populations, and cytokine levels (IL-17, IL-6).
- Investigated STAT3 phosphorylation and therapeutic intervention with a STAT3 inhibitor.
Main Results:
- p53(null)CD45.1 mice spontaneously developed autoimmunity with increased Th17 effectors and elevated IL-17 and IL-6.
- p53-deficient T cells showed heightened sensitivity to IL-6-induced STAT3 phosphorylation.
- STAT3 inhibition suppressed Th17 effectors and alleviated autoimmune symptoms.
Conclusions:
- p53 activity in T cells suppresses autoimmunity by controlling Th17 effector differentiation.
- The p53-STAT3-Th17 axis is a critical regulator of immune homeostasis.
- Targeting the p53-STAT3-Th17 pathway offers potential therapeutic strategies for autoimmune diseases.
Related Concept Videos
01:24T 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...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
02:23Abnormal 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...
01:25Inflammatory Bowel Disease III: Crohn's Disease
Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...