Targeting Th17 cells in autoimmune diseases.

Area of Science:

• Immunology
• Autoimmune Diseases
• Cellular Biology

Background:

• T helper 17 (Th17) cells are implicated in autoimmune diseases like psoriasis, rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and multiple sclerosis (MS).
• While anti-interleukin-17 (IL-17) therapies are effective for psoriasis, they are insufficient for RA and Crohn's disease.
• Th17 cells produce multiple pro-inflammatory cytokines beyond IL-17, including IL-17F, IL-22, IL-26, and granulocyte-macrophage colony-stimulating factor (GM-CSF).

Purpose of the Study:

• To discuss the rationale for targeting two key checkpoints in Th17 cell development and function: retinoid-related orphan receptor-γt (RORγt) and IL-23.
• To review advancements in developing therapeutic agents against these targets.

Main Methods:

• Review of scientific literature on Th17 cell biology and autoimmune disease pathogenesis.
• Analysis of current therapeutic strategies targeting IL-17 and emerging strategies targeting RORγt and IL-23.

Main Results:

• Targeting the Th17 cell lineage, rather than a single cytokine, is proposed as a potentially superior therapeutic strategy.
• Progress has been made in developing small molecule inhibitors for RORγt and neutralizing antibodies for IL-23.

Conclusions:

• Targeting RORγt and IL-23 represents a promising approach for treating a broader range of autoimmune diseases.
• Further development of RORγt inhibitors and IL-23 antibodies is warranted to improve clinical outcomes in autoimmune conditions.