HSP70, a Novel Regulatory Molecule in B Cell-Mediated Suppression of Autoimmune Diseases.
J Mol Biol
; 433(1): 166634, 2021 01 08.
Article
en En
| MEDLINE
| ID: mdl-32860772
ABSTRACT
B cells have recently emerged as playing regulatory role in autoimmune diseases. We have previously demonstrated that human peripheral blood CD19+CD24hiCD27+ B cells have regulatory function both in healthy donors and in patients with autoimmune disease. However, the mechanism of this regulation is still not fully understood. In this study, microarrays were utilized to compare gene expression of CD19+CD24hiCD27+ B cells (regulatory B cells, Bregs) with CD19+CD24loCD27- B cells (non-Bregs) in human peripheral blood. We found that heat shock protein 70 (HSP70) expression was significantly upregulated in Bregs. In vitro studies explored that HSP70 inhibition impaired the regulatory function of peripheral blood Bregs. In mouse models of autoimmune disease, using HSP70-deficient mice or HSP70 inhibitors, Bregs suppressed effector cells and rescued disease-associated phenotypes that were dependent on HSP70. Mechanistically, Bregs secreted HSP70, directly suppressing effector cells, such as T effect cells. These findings reveal that HSP70 is a novel factor that modulates Breg function and suggest that enhancing Breg-mediated production of HSP70 could be a viable therapy for autoimmune disease.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Autoinmunes
/
Linfocitos B
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Proteínas HSP70 de Choque Térmico
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Susceptibilidad a Enfermedades
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Inmunomodulación
Tipo de estudio:
Diagnostic_studies
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Etiology_studies
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Prognostic_studies
Límite:
Adult
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Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Mol Biol
Año:
2021
Tipo del documento:
Article