The emerging role of T helper 9 (Th9) cells in immunopathophysiology: A comprehensive review of their effects and responsiveness in various disease states

Abstract

Th9 cells, a subset of T-helper cells producing interleukin-9 (IL-9), play a vital role in the adaptive immune response and have diverse effects in different diseases. Regulated by transcription factors like PU.1 and IRF4, and cytokines such as IL-4 and TGF-β, Th9 cells drive tissue inflammation. This review focuses on their emerging role in immunopathophysiology. Th9 cells exhibit immune-mediated cancer cell destruction, showing promise in glioma and cervical cancer treatment. However, their role in breast and lung cancer is intricate, requiring a deeper understanding of pro- and anti-tumor aspects. Th9 cells, along with IL-9, foster T cell and immune cell proliferation, contributing to autoimmune disorders. They are implicated in psoriasis, atopic dermatitis, and infections. In allergic reactions and asthma, Th9 cells fuel pro-inflammatory responses. Targeting Foxo1 may regulate innate and adaptive immune responses, alleviating disease symptoms. This comprehensive review outlines Th9 cells’ evolving immunopathophysiological role, emphasizing the necessity for further research to grasp their effects and potential therapeutic applications across diseases.

PLAIN LANGUAGE SUMMARY

The immune system relies on CD4⁺ T cells, specifically Th9 cells, which produce Interleukin-9 (IL-9) to combat infections. Th9 cells have distinct functions regulated by various factors and are implicated in diseases, including cancer. Preclinical studies suggest Th9 cells could target tumors, but their role in cancer remains intricate. In lung and breast cancer, Th9 cells influence tumor growth and immune responses. Glioma research explores inducing Th9 cells to inhibit brain tumor growth. Th9 cells exhibit both positive and negative associations with colorectal cancer, lymphoma, and melanoma. Investigation into Th9 cells extends to autoimmune diseases like Graves’ disease, inflammatory bowel disease, psoriasis, lupus, scleroderma, rheumatoid arthritis, and multiple sclerosis, where they may contribute to inflammation. In atopic dermatitis, elevated IL-9 levels correlate with disease severity, indicating Th9 cells’ involvement in inflammation and cell activation. The complexity of Th9 cells underscores the necessity for disease-specific therapies. Understanding Th9 cells and IL-9 is pivotal for developing targeted treatments, emphasizing the nuanced role these cells play in diverse diseases and the potential for tailored therapeutic approaches.

Graphical Abstract

Keywords:

• Adaptive immune response
• autoimmune disorders
• immunopathophysiology
• interleukins-9
• Th9 cells

Declaration of Interest

The authors have no relevant financial or non-financial interests to declare.

Code availability

Not applicable.

Ethics approval

Not applicable.

Consent to participate

For this review article, informed consent was not necessary.

Consent for publication

Not applicable.

Author contributions

Study concept and design: PP, MK; acquisition of data: MK; statistical analysis and interpretation of data: MK, PP; data visualization: MK; drafting of the manuscript: PP, MK; critical revision of the manuscript: PP; study supervision: PP.

Data availability statement

The data that support the findings of this study are available from the corresponding author, [PP], upon reasonable request.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.