Integrin α3 promotes TH17 cell polarization and extravasation during autoimmune neuroinflammation.
Eunchong Park1,2, William E Barclay1, Alejandro Barrera2,3
1Department of Integrative Immunobiology, Duke University Medical Center, Durham, NC, USA.
Science Immunology
|October 13, 2023
Summary
Integrin alpha3 is crucial for pathogenic T helper 17 (TH17) cells in multiple sclerosis (MS). Blocking integrin alpha3 may offer a new therapeutic strategy for MS by preventing TH17 cell migration.
Area of Science:
- Neuroimmunology
- Cellular Immunology
- Autoimmune Diseases
Background:
- Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune disease.
- T helper 17 (TH17) cells are key drivers of MS pathogenesis.
- Current therapies targeting leukocyte trafficking lack specificity for encephalitogenic TH17 cells.
Purpose of the Study:
- To identify novel therapeutic targets for MS.
- To investigate the role of integrin α3 in TH17 cell pathogenicity.
- To explore integrin α3 as a specific blocker of TH17 cell migration.
Main Methods:
- Utilized experimental autoimmune encephalomyelitis (EAE) models.
- Assessed the expression of integrin α3 in CNS-infiltrating TH17 cells.
- Investigated the impact of integrin α3 deletion in CD4+ T cells and Il17a fate-mapped cells on disease severity.
- Analyzed the effect of integrin α3 on immunological synapse formation, TH17 cell proliferation, and transmigration across the blood-brain barrier.
Main Results:
- CNS-infiltrating TH17 cells exhibit high expression of integrin α3.
- Deletion of integrin α3 in CD4+ T cells or Il17a fate-mapped cells significantly attenuated EAE disease severity.
- Integrin α3 was found to enhance TH17 cell polarization, proliferation, and immunological synapse formation.
- TH17 cell transmigration into the CNS was dependent on integrin α3, with deficiency leading to enhanced CD4+ T cell retention in the perivascular space.
- Integrin α3 maintains TH17 cell identity and effector functions.
Conclusions:
- Integrin α3 is a critical determinant of TH17 cell pathogenicity in MS.
- Integrin α3 plays a vital role in TH17 cell migration into the CNS.
- Integrin α3 represents a promising and specific therapeutic target for MS treatment.
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