Suppresses ‘STAT3–IL-17’ inflammatory signaling by restoring mitochondrial function

Effectiveness confirmed in animal models and patient immune cells, presenting a new strategy for preventing recurrence

△ (From left) Professor Mi-La Cho (Dept. of Pathology), Professor Chul Hwan Bang (Dept. of Biomedicine & Health Sciences), and Graduate Student Tae-Ho Kim (Dept. of Medical Science)

A research team led by Professor Mi-La Cho (Co-corresponding author) from the Department of Pathology at The Catholic University of Korea (CUK) College of Medicine has proposed a new therapeutic possibility to control the root cause of psoriasis, a chronic skin disease characterized by frequent recurrence.

The study involved Professor Chul Hwan Bang (Co-corresponding author) from the Department of Dermatology at Seoul St. Mary’s Hospital and graduate student Tae-Ho Kim (First author) from the Department of Medical Science at CUK.

Psoriasis is a chronic autoimmune disease causing red rashes, scales, itching, and pain. It occurs when immune cells become overactive, leading to persistent inflammation. The cycle of recurrence and aggravation imposes significant physical and mental burdens on patients, sometimes leading to social isolation and depression.

A key player in this process is the ‘CD8 tissue-resident memory T cell (CD8 TRM).’ These cells remain in skin tissues for long periods and "remember" inflammation. Even after surface symptoms disappear, these cells persist and trigger re-inflammation, causing the disease to recur easily.

The central driver of this process is ‘IL-17,’ an inflammatory cytokine. When CD8 TRM cells secrete excessive IL-17, inflammation worsens. The team investigated why these immune cells remain hyperactivated.

The researchers focused on ‘mitochondria,’ the cell’s "powerhouse." In the CD8 TRM cells of psoriasis patients, mitochondrial functions were abnormally altered: reactive oxygen species (ROS) increased excessively, while the oxygen consumption rate (OCR) decreased.

These changes cause the signaling protein ‘STAT3’ to become overactive, ultimately promoting IL-17 secretion. This is known as the ‘Mitochondria–STAT3–IL-17 axis.’ In short, malfunctions in the cellular energy factory create a vicious cycle that amplifies inflammatory signals.

The team utilized ‘Nano Graphene Oxide (NGO),’ a carbon-based nanomaterial. Through joint research with InBCT Co., Ltd., they devised a method to stably deliver NGO into cells to regulate their functions.

Experimental results showed that NGO treatment led to:

• Reduction of increased ROS

• Restoration of impaired mitochondrial function

• Decrease in hyperactivated STAT3 (pSTAT3)

• Reduction in the number of IL-17-secreting cells

This indicates that NGO does not simply suppress inflammation but cuts off the fundamental inflammatory signal by normalizing the energy metabolism of immune cells.

The team confirmed these effects in psoriasis-induced mouse models. While inflammation-related cells and IL-17 expression were high in untreated models, the group treated with NGO showed a significant reduction in inflammatory cells and a clear improvement in the Psoriasis Area and Severity Index (PASI).

Professor Mi-La Cho stated, “This study confirms that metabolic abnormalities in CD8 TRM cells, which cause psoriasis recurrence, can be regulated at the mitochondrial level. This will serve as a new therapeutic strategy that blocks the fundamental signals of disease recurrence rather than just suppressing inflammation.”

Furthermore, identical results were confirmed in immune cells (PBMC) isolated from actual psoriasis patients. After NGO treatment, mitochondrial functions returned to normal levels, and the proportion of IL-17-secreting immune cells significantly decreased.

Professor Chul Hwan Bang added, “While some existing treatments inhibit JAK-STAT signals, issues such as decreased efficacy or resistance during long-term use have been reported. This research is distinctive as it suggests a new approach by regulating the energy metabolism of immune cells itself.”

The study was published in the Journal of Nanobiotechnology (Impact Factor 12.6), a prestigious international journal in nanotechnology-based immune research, titled: “NGO ameliorates psoriasis by modulating mitochondrial function and suppressing pSTAT3–IL-17–expressing CD8+ TRM cells.”

△Investigation of mitochondrial homeostasis and STAT3-IL-17 signaling regulation in NGO-mediated IL-17 expressing immune cells.

△Investigation of the therapeutic effect of NGO in a psoriasis mouse model through the suppression of the STAT3-IL-17 axis-mediated CD8+ TRM cells.

△Investigation of mitochondrial function recovery and STAT3-IL-17 axis suppression in psoriasis patient-derived immune cells by NGO.

△Summary Graphic.