Related Experiment Videos

TOLLIP Inhibits Psoriasis Progression via Suppressing PKM2-Mediated Glycolysis in Keratinocytes

Xiuhuan Jiang1, Guoying Miao2, Na Shen2

  • 1Baoding Key Laboratory of Cancer & Aging, College of Life Science, Hebei University, Baoding, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|July 31, 2026
PubMed

Insights

Toll-interacting protein (TOLLIP) regulates psoriasis by controlling aerobic glycolysis. Inhibiting this metabolic pathway with TOLLIP reduces inflammation and keratinocyte hyperproliferation, offering a new therapeutic target for psoriasis.

Area of Science:

  • Dermatology
  • Metabolic pathways
  • Molecular biology

Background:

  • Aerobic glycolysis is a key mechanism in psoriasis pathogenesis.
  • The precise regulatory mechanisms of this metabolic reprogramming remain unclear.

Purpose of the Study:

  • To identify critical regulators of glycolytic metabolism in psoriasis.
  • To elucidate the role of Toll-interacting protein (TOLLIP) in psoriasis pathogenesis.

Main Methods:

  • Analysis of TOLLIP expression in psoriatic lesions.
  • Utilizing imiquimod (IMQ)-induced psoriasis mouse models with TOLLIP genetic deletion.
  • Investigating the interaction between TOLLIP and pyruvate kinase M2 (PKM2).
  • Therapeutic intervention using adeno-associated virus (AAV) vectors delivering TOLLIP.

Main Results:

  • TOLLIP is significantly upregulated in psoriatic lesions.
  • Genetic deletion of TOLLIP exacerbated IMQ-induced psoriasis.
  • TOLLIP interacts with PKM2, inhibiting its activity and attenuating aerobic glycolysis.
  • AAV-mediated delivery of TOLLIP ameliorated psoriasis progression in mice.

Conclusions:

  • The TOLLIP-PKM2-glycolysis axis is a key mechanism linking metabolic reprogramming to psoriasis.
  • TOLLIP acts as a critical regulator of psoriasis pathogenesis by modulating glycolytic metabolism.
  • TOLLIP presents a promising therapeutic target for psoriasis treatment.
Keywords:
CUEGlycolysisPKM2PsoriasisTOLLIP

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/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...
The JAK-STAT Signaling Pathway01:20

The 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...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
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...
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
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...