TH17 Cells in Autoimmunity and Immunodeficiency: Protective or Pathogenic?

Area of Science:

• Immunology
• Cell Biology
• Human Pathology

Background:

• Th17 cells, identified in 2005, were initially implicated in autoimmune and auto-inflammatory diseases.
• Discoveries in primary immunodeficiencies revealed Th17 cells' crucial role in combating fungal and bacterial infections.
• Clinical trials of IL-17A inhibitors showed paradoxical worsening of Crohn's disease, questioning Th17's universally detrimental role.

Purpose of the Study:

• To review the dual role of Th17 cells in human diseases.
• To explore how environmental factors influence Th17 cell differentiation and function.
• To summarize evidence on context-dependent protective versus pro-inflammatory functions of Th17 cells.

Main Methods:

• Review of clinical data from patients with immunodeficiencies.
• Analysis of evidence from autoimmune and auto-inflammatory disease studies.
• Synthesis of findings on Th17 cell differentiation and function in various human diseases.

Main Results:

• Th17 cells exhibit plasticity, differentiating into either protective or pro-inflammatory phenotypes.
• The specific disease environment dictates whether Th17 cells promote or protect against pathology.
• Evidence from human diseases demonstrates context-specific roles for Th17 cells.

Conclusions:

• Th17 cell function is not uniformly pro-inflammatory; it is highly dependent on the disease context.
• Understanding the environmental cues that direct Th17 cell differentiation is critical for therapeutic strategies.
• The dual role of Th17 cells necessitates tailored approaches in treating immune-related disorders.