Researchers are learning more about how the immune system may contribute to the severity of some forms of congenital ichthyosis.
Ichthyosis is a group of rare genetic skin disorders that affect how the skin develops, forms its protective barrier, and sheds. While researchers have long understood that genetic changes play an important role in ichthyosis, they are continuing to learn how the immune system and inflammation may also contribute to the symptoms people experience.
A new study published in the Indian Journal of Dermatology, Venereology and Leprology looked at a specific part of the immune system called the IL-23/Th17 pathway. The researchers found increased activity in this pathway among people with several forms of congenital ichthyosis, particularly autosomal recessive congenital ichthyosis (ARCI) and Netherton syndrome (NS). They also found that higher levels of certain inflammatory signals were associated with greater disease severity.
What is the IL-23/Th17 pathway?
The immune system uses many different cells and chemical messengers to communicate. Some of these messengers are called interleukins, or ILs.
Think of interleukins as messages that immune cells send to one another. They can help the body fight infections and respond to injury. However, when certain inflammatory signals remain active, they can also contribute to inflammation.
This study focused on two of these signals:
- IL-23
- IL-17A
They are part of a connected immune response involving Th17 cells, a type of immune cell.
In simple terms, the researchers wanted to know whether this immune pathway is more active in people with congenital ichthyosis, and whether that activity is related to how severe their skin disease is.
What did the researchers study?
The study included 48 people with congenital ichthyosis and 34 healthy controls. Most of the participants with ichthyosis had ARCI, while others had Netherton syndrome, X-linked recessive ichthyosis (XLRI), keratinopathic ichthyosis, or other diagnoses. The study was conducted at a medical center in Chandigarh, India.
Researchers examined blood and skin samples and looked at several immune-related markers. They also compared these findings with measures of skin disease severity, including redness, scaling, the amount of skin affected, and an overall ichthyosis severity score.
What did they find?
One of the most notable findings was increased IL-17A activity.
IL-17A was increased in the blood of people with several forms of ichthyosis, with the largest increase seen in the ARCI group. The researchers also found increased IL-17A in skin samples from people with ichthyosis compared with healthy controls.
The researchers found increased IL-23 gene activity as well, particularly in ARCI and Netherton syndrome. However, the amount of IL-23 detected in the blood was not consistently elevated across all of the ichthyosis groups.
Another interesting finding was that IL-22, another immune messenger associated with the Th17 pathway, was significantly higher in the small group of participants with XLRI.
The researchers also found a relationship between IL-17A activity and some measures of disease severity. In particular, higher IL-17A activity was associated with increased redness (erythema) and higher overall ichthyosis severity scores.
Why does this matter?
For people living with ichthyosis, it can sometimes seem like the skin is simply “dry” or “thick”. Researchers now know that the biology of ichthyosis is much more complicated.
Genetic changes can affect the skin barrier and the way skin cells develop and shed. These changes may also trigger immune responses in the skin. Previous research has similarly identified increased activity involving IL-17 in several forms of ichthyosis and found relationships between this inflammatory activity and disease severity.
This newer study adds to that growing body of evidence by showing that the IL-23/Th17 pathway is not affected in exactly the same way in every type of ichthyosis.
That distinction is important. Ichthyosis includes many different genetic conditions, and what happens in one type may not happen in another.
Could this lead to new treatments?
The findings raise an interesting possibility for future research.
There are already medicines that target IL-17 or IL-23 pathways for other inflammatory skin diseases. Because this study and earlier research suggest that these pathways may be involved in inflammation associated with some forms of ichthyosis, researchers are interested in whether targeting these pathways could eventually have a role in treatment.
However, this study does not show that IL-17- or IL-23-targeting medicines are effective or approved treatments for ichthyosis. More research, including clinical trials, is needed to determine whether these approaches are safe and beneficial for people with specific types of ichthyosis.
It is also important to remember that reducing inflammation would not necessarily correct the underlying genetic cause of ichthyosis. Future treatments may need to address multiple parts of the disease, including problems with skin-cell development, the skin barrier, scaling, and inflammation.
What comes next?
The researchers noted several limitations. The study was relatively small, particularly for some of the less common ichthyosis subtypes. In addition, the researchers were not able to perform a complete analysis of messenger RNA and cytokine activity directly in the skin biopsy samples.
Larger studies involving more people and a wider range of ichthyosis types will be important to determine whether these findings apply broadly across the ichthyosis community.
The bigger picture
Every study that helps researchers understand why ichthyotic skin behaves the way it does brings us one step closer to more targeted treatments.
This research suggests that inflammation and immune-system activity may be an important piece of the puzzle for certain forms of congenital ichthyosis. It also reinforces an important point: ichthyosis is more than a problem with dry or scaly skin. It involves complex changes in the biology of the skin and, in some forms, the body’s immune response.
As researchers continue to uncover these connections, the hope is that a better understanding of the disease will lead to more personalized and effective treatment options for people living with ichthyosis.
https://medicaldialogues.in/dermatology/news/il-23th17-pathway-activation-linked-to-disease-severity-in-congenital-ichthyosis-study-176702
Source: Kumar A, Mahajan R, Srivastava N, et al. Patients with congenital ichthyosis show differential activation of IL-23/Th17 pathway among various disease subtypes – A single-centre experience. Indian Journal of Dermatology, Venereology and Leprology. 2026;92:319-327. DOI: 10.25259/IJDVL_1749_2024
