Harnessing Treg Cells for their Therapeutic Potential — The Basics & Opportunities to Drive Drug Discovery & Development
Eurofins DiscoverX® extends our sincere congratulations to the Nobel Prize winners of 2025 in Physiology or Medicine, Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi. Their groundbreaking work on Regulator T (Treg) cells and the transcription factor FoxP3 has significantly advanced our understanding of immune regulation. The Nobel Prize recognition of Tregs as a pivotal node in immune tolerance is a testament to their profound impact on the field.
The Basics
Treg cells are specialized CD4+ T cells that function to maintain self-tolerance and immune homeostasis by suppressing the activation, proliferation, and effector functions of various immune cells. Tregs are characterized by expression of the transcription factor FoxP3 and high surface expression of CD25 (IL-2Rα). By suppressing effector T cell activity, limiting cytokine release, and shaping tissue-microenvironmental immunity, Tregs serve as key guardians of homeostasis and are commonly referred to as “peacekeepers” of the immune system. Their significance in therapeutic development has been underscored by the emergence of therapeutics aimed at enhancing Treg numbers or function, and, conversely, targeting Treg suppression. A better understanding of the mechanisms by which Treg cells exert their suppressive function has broad implications for the discovery and development of therapies for cancer, diabetes, and autoimmune diseases. The Nobel recognition underscores how far the field has progressed from foundational immunology to translational potential.
Figure 1. Treg/Th17 axis depicting cytokines for targeting therapeutics at aiming to restore immune balance favoring Treg cells over Th17 cells.
As Tregs do not operate in isolation, one of the most compelling mechanistic interactions in recent years is between Tregs and the pro-inflammatory CD4+ T cell subset, T helper 17 (Th17) cells. Th17 cells are defined by the expression of the transcription factor RORγt and the production of IL-17 family cytokines that drive inflammatory responses in barrier tissues and contribute to numerous autoimmune disorders. The differentiation of naïve CD4+ T cells into either Tregs or Th17 is closely linked and dynamically regulated by various cytokines. For example, TGF-β plus IL-6/IL-21 favors Th17 cell differentiation, whereas TGF-β alone favors Treg cell differentiation. In this sense, Tregs and Th17 cells represent two sides of a regulatory coin: Tregs aim to dampen immune activation, whereas Th17 cells tilt the balance toward inflammation. This dynamic interplay means that therapeutic strategies aiming to restore immune balance often target the Treg/Th17 axis, favoring tolerance (Treg) or dampening inflammation (Th17), as appropriate.
Opportunities
From a drug discovery and development perspective, the interplay between Treg and Th17 biology presents significant opportunities and challenges. Eurofins DiscoverX, with the extensive portfolio of mechanism of action (MOA) reflective cytokine receptors, is uniquely positioned to enable researchers to explore functional receptor-ligand interactions and ligand/inhibitor activities in the context of immune-modulatory targets. The PathHunter® dimerization assays and cell lines, which allow the quantification of receptor subunit assembly, are particularly suited for the quantitative assessment of activation or inhibition of pathways relevant to Treg and Th17 biology to support various therapeutic strategies.
- Inhibition of Th17 cells: Targeting pro-inflammatory cytokines like IL-17 or using antibodies or small molecules that block Th-17 related pathways.
- Promoting Treg cell differentiation: Utilizing cytokines like IL-27 to promote cell differentiation and suppress Th17 development.
These phase-appropriate functional, cell-based assays are ideal for the discovery, pre-clinical development, and commercial release testing of therapeutic biologics or small molecules targeting cytokine receptors. As the industry increasingly focuses on immune modulation to enhance Treg function, inhibit pathogenic Th17 activity, or restore homeostasis, the ability to measure and quantify receptor activity in a physiological cellular context becomes invaluable.
Eurofins DiscoverX’s offering in the Th17 repertoire (covering IL-17, IL-23, and IL-6 systems) alongside the broader cytokine-receptor panel, is uniquely positioned to support your programs in this area that aim to reset the Treg/Th17 balance. Whether the objective is to enhance Treg signaling or to attenuate Th17/IL-17-driven inflammation, these assays provide the functional linkage between receptor engagement and downstream outcomes.
Resource: Access a full repertoire of cytokine receptor product solutions to accelerate therapeutic development of targets involved in Treg/Th17 axis.
Once again, we extend our congratulations to Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi on this well-deserved recognition of their enduring contributions. We are committed to supporting your continued work in this field and look forward to the future advancements you will bring.