miR-147-3p in pathogenic CD4 T cells controls chemokine receptor expression for the development of experimental autoimmune diseases
Incomplete Freund's adjuvant (IFA) has long been used to trigger autoimmune diseases in animal models, such as experimental autoimmune encephalitis and collagen-induced arthritis. However, the molecular mechanisms that control CD4 T cell effector functions and lead to the development of autoimmune diseases are not well understood. A self-antigen and heat-killed Mycobacterium tuberculosis emulsified in IFA augmented the activation of CD4 T cells, leading to the differentiation of pathogenic CD4 T cells in the draining lymph nodes. In contrast, IFA emulsification did not elicit Foxp3<sup>+</sup> regulatory T cell expansion. We found that pathogenic Th1 cells expressed miR-147-3p, which targets multiple genes to affect T cell function. Finally, miR-147-3p expressed in CXCR6<sup>+</sup>SLAMF6<sup>-</sup> Th1 cells was required for the onset of neurological symptoms through the control of CXCR3 expression. Our findings demonstrate that miR-147-3p expressed in pathogenic CD4 T cells regulates the migratory potential in peripheral tissues and impacts the development of autoimmune diseases.
Authors
- Tatsusada Okuno (ORCID: https://orcid.org/0000-0002-1208-936X)
- Masaaki Niino (ORCID: https://orcid.org/0000-0001-5722-920X)
- M. Yamaguchi (ORCID: https://orcid.org/0000-0001-6218-7112)
- Osamu Suzuki (ORCID: https://orcid.org/0000-0002-9003-7282)
- Norifumi Iijima (ORCID: https://orcid.org/0009-0001-1329-0831)
- Yuta Ohira (ORCID: https://orcid.org/0000-0001-7800-3736)
- Ken J. Ishii (ORCID: https://orcid.org/0000-0002-6728-3872)
- Tomoya Hayashi (ORCID: https://orcid.org/0000-0003-3189-6463)
- Yuxiang Rui
- Yoichi Miyamoto (ORCID: https://orcid.org/0000-0003-4016-1119)
- Masahiro Oka (ORCID: https://orcid.org/0000-0003-0123-3060)
Institutions
- National Institute of Biomedical Innovation, Health and Nutrition (JP)
- National Hospital Organization Hokkaido Medical Center (JP)
- Zeria Pharmaceutical (Japan) (JP)
- The University of Osaka (JP)
Publication Details
- Journal
- Journal of Autoimmunity
- Published
- 2024-10-11
- DOI
- https://doi.org/10.1016/j.jaut.2024.103319
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Bristol-Myers Squibb
- Takeda Science Foundation
- Uehara Memorial Foundation
- Japan Agency for Medical Research and Development
- Taiju Life Social Welfare Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Daiichi Sankyo Foundation of Life Science
- Astellas Foundation for Research on Metabolic Disorders
- NOVARTIS Foundation (Japan) for the Promotion of Science
- Core Research for Evolutional Science and Technology