CRIg, a tissue-resident macrophage specific immune checkpoint molecule, promotes immunological tolerance in NOD mice, via a dual role in effector and regulatory T cells
- University of California, San Diego, United States
Abstract
How tissue-resident macrophages (TRM) impact adaptive immune responses remains poorly understood. We report a novel mechanism by which TRMs regulate T cell activities at tissue sites. This mechanism was mediated by the complement receptor of immunoglobulin family (CRIg). Using animal models for autoimmune type 1 diabetes (T1D), we found that CRIg+ TRMs form a protective barrier surrounding pancreatic islets. Genetic ablation of CRIg exacerbated islet inflammation and local T cell activation. CRIg exhibited a dual function of attenuating early T cell activation and promoting the differentiation of Foxp3+ regulatory (Treg) cells. More importantly, CRIg stabilized the expression of Foxp3 in Treg cells, by enhancing their responsiveness to interleukin-2. The expression of CRIg in TRMs was postnatally regulated by gut microbial signals and metabolites. Thus, environmental cues instruct TRMs to express CRIg, which functions as an immune checkpoint molecule to regulate adaptive immunity and promote immune tolerance.
Article and author information
Author details
Funding
American Association of Immunologists
- Xiaomei Yuan
JDRF (2-SRA-2016-306-S-B)
- Wenxian Fu
National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK063491)
- Wenxian Fu
University of California, San Diego (UL1 TR000100)
- Wenxian Fu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All mice were housed under specific pathogen free (SPF) conditions in our animal facility at University of California, San Diego, in accordance with the ethical guidelines of the Institutional Animal Care and Use Committee (#S13253).
Copyright
© 2017, Yuan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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CRIg, a tissue-resident macrophage specific immune checkpoint molecule, promotes immunological tolerance in NOD mice, via a dual role in effector and regulatory T cells
eLife 6:e29540.
https://doi.org/10.7554/eLife.29540
