image_3_Interleukin-10 Producing Regulatory B Cells Transformed CD4+CD25− Into Tregs and Enhanced Regulatory T Cells Function in Human Leprosy.tif
Regulatory B cells (Bregs) are known to exhibit their regulatory functions through interleukin-10 (IL-10) cytokine which suppress inflammation. There are only a few studies explaining the phenotype and functioning of these cells in contribution to host immunity in leprosy. Here, we evaluated the role of IL-10 producing Bregs in the pathogenesis of leprosy and assessed their immunoregulatory effects on Tregs and effector T cells. We found an increased frequency of Bregs and increased expression of their immune modulatory molecules (IL-10, FoxP3, and PDL-1) in leprosy patients. The potential immunoregulatory mechanism of Bregs was also investigated using MACS sorted Teff (CD4+CD25−) and Treg (CD4+CD25+) cells were cocultured with Bregs to elucidate the effects of Bregs on effector T and regulatory T cells. Cell coculture results showed that purified Bregs cells from leprosy patients convert CD4+CD25− cells into CD4+CD25+ cells. Cell coculture experiments also demonstrated that leprosy derived IL-10 producing Bregs enhance FoxP3 and PD-1 expression in Tregs and enhanced Tregs activity. Blocking of IL-10 receptor confirmed that IL-10 producing Breg has immunomodulatory effect on Tregs and effector T cells as effector T cells are not converted into Tregs and enhanced expression of FoxP3 and PD-1 was not observed on Tregs. Collectively, these findings demonstrate that IL-10 producing Breg cells play an important mechanism in controlling the immunopathogenesis of leprosy and have an immunomodulatory effect on Tregs and effector T cells. Our findings may pave way for novel targets of IL-10 producing Bregs for immunotherapy in leprosy patients.
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References
- https://doi.org//10.1126/science.1925582
- https://doi.org//10.1126/science.1681588
- https://doi.org//10.1016/j.clim.2011.06.007
- https://doi.org//10.1016/j.cyto.2016.12.011
- https://doi.org//10.1016/j.molimm.2017.01.008
- https://doi.org//10.1111/exd.13302
- https://doi.org//10.2174/1389203718666170829120729
- https://doi.org//10.1016/j.imlet.2017.02.013
- https://doi.org//10.4049/jimmunol.176.2.705
- https://doi.org//10.1084/jem.184.6.2271
- https://doi.org//10.4049/jimmunol.172.6.3422
- https://doi.org//10.4049/jimmunol.170.12.5897
- https://doi.org//10.4049/jimmunol.1001307
- https://doi.org//10.1002/eji.200940288
- https://doi.org//10.1084/jem.20021293
- https://doi.org//10.1038/ni833ni833
- https://doi.org//10.1002/eji.201040673
- https://doi.org//10.4049/jimmunol.167.2.1081
- https://doi.org//10.2174/1573395511666141204224229
- https://doi.org//10.1016/j.cyto.2015.01.014
- https://doi.org//10.1371/journal.pntd.0004338
- https://doi.org//10.1111/j.1600-065X.2010.00923.x
- https://doi.org//10.1038/cmi.2015.10
- https://doi.org//10.1371/journal.pntd.0002639
- https://doi.org//10.1016/j.oraloncology.2015.11.003
- https://doi.org//10.1016/j.immuni.2011.03.018
- https://doi.org//10.1016/j.imbio.2013.05.004
- https://doi.org//10.1084/jem.174.5.1209
- https://doi.org//10.1038/ni.1791
- https://doi.org//10.1155/2017/8415094
- https://doi.org//10.1371/journal.pntd.0006121
- https://doi.org//10.1007/s12016-016-8572-510.1007/s12016-016-8572-5
- https://doi.org//10.1016/j.autrev.2011.11.018
- https://doi.org//10.1126/scitranslmed.3003130
- https://doi.org//10.4049/jimmunol.1002939
- https://doi.org//10.1089/jir.2006.0144
- https://doi.org//10.1203/PDR.0b013e31819e76c7
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Categories
- Transplantation Immunology
- Tumour Immunology
- Immunology not elsewhere classified
- Immunology
- Veterinary Immunology
- Animal Immunology
- Genetic Immunology
- Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
- Autoimmunity
- Cellular Immunology
- Humoural Immunology and Immunochemistry
- Immunogenetics (incl. Genetic Immunology)
- Innate Immunity