Human mast cells capture, store, and release bioactive, exogenous IL-17A

Area of Science:

• Immunology
• Cell Biology
• Pathology

Background:

• Interleukin-17A (IL-17A) is a critical pro-inflammatory cytokine implicated in various human inflammatory diseases.
• The precise cellular origin of IL-17A in these conditions, particularly from mast cells, has been a subject of debate, with conflicting evidence from human and murine studies.

Purpose of the Study:

• To investigate the cellular source and mechanism of IL-17A involvement in human inflammatory diseases.
• To clarify the role of mast cells in the context of IL-17A-driven inflammation.

Main Methods:

• Analysis of IL-17A protein localization in human inflamed tissues.
• Investigation of IL-17A uptake and storage mechanisms in primary human mast cells.
• Assessment of IL-17A release from mast cells.

Main Results:

• Human mast cells do not produce IL-17A but actively internalize exogenous IL-17A via receptor-mediated endocytosis.
• Internalized IL-17A is stored within intracellular granules.
• Mast cells can release this stored IL-17A in a bioactive form, contributing to inflammation.

Conclusions:

• Human mast cells act as reservoirs for IL-17A, capturing and releasing it to modulate tissue inflammation.
• This mechanism provides a novel explanation for the presence of IL-17A in inflamed tissues and highlights mast cells as key regulators of IL-17A-mediated inflammatory responses.