A lymphocyte chemoaffinity axis for lung, non-intestinal mucosae and CNS

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Lymphocytes use chemoattractants to establish local immune environments at epithelial surfaces.
• Mechanisms guiding lymphocytes to respiratory and other non-intestinal mucosal tissues are not well understood.
• Previous research identified chemoattractants for intestinal and skin tissues.

Purpose of the Study:

• To identify chemoattractant mechanisms for non-intestinal mucosal tissues.
• To elucidate the role of GPR25 and CXCL17 in lymphocyte homing.
• To understand the implications for immunity, tolerance, and autoimmunity.

Main Methods:

• Analysis of diverse omics datasets.
• Single-cell transcriptomic analysis.
• Mouse models of lymphocyte homing.
• Human tissue analysis.

Main Results:

• GPR25 identified as a lymphocyte receptor for CXCL17.
• CXCL17 expression unifies airways, upper GI, and squamous mucosae.
• GPR25 is imprinted on lymphocytes in secondary lymphoid tissues and characterizes tissue-resident memory and regulatory T cells.
• GPR25-CXCL17 axis mediates lymphocyte homing to various non-intestinal barrier epithelia and CNS.
• GPR25 imprinting on regulatory T cells links to autoimmunity protection.

Conclusions:

• A novel GPR25-CXCL17 chemoaffinity axis is defined for non-intestinal mucosal tissues and the CNS.
• This axis integrates immunity and tolerance at barrier surfaces.
• The findings provide insights into lymphocyte trafficking and potential therapeutic targets for autoimmune diseases.