Role of Regulatory B Cell subsets in Non-infectious Uveitis
Purpose
The role of regulatory B lymphocytes (Bregs) is not clearly known in Non-infectious uveitis (NIU) and experimental autoimmune uveitis (EAU) models. This study investigates Breg subsets in uveitis.
Methods
Blood samples from NIU patients and healthy controls were studied for the immature transitional (IT) and primarily mature Bregs subsets. Furthermore, EAU was established and compared to mice receiving antibiotic treatment (ABX) and Mycobacterium tuberculosis (MTB) for B10, B-1, transitional 2 marginal-zone precursor (T2-MZP), and marginal-zone B (MZB) Bregs. The proliferation of T cells were used to invesitate the immunosuppressive function of Breg cells.
Results
In NIU, the presence of IL-10+ IT and B10 Breg was associated with disease remission (P < 0.05). During peak EAU, only IL-10+ splenic B10 cells were inversely correlated with EAU severity (P = 0.048, R2 = 0.47). In the retina, only the B10 subset was detected, and evident at peak EAU. The B10 Bregs from only EAU primed mice and IT Bregs from inactive NIU patients were functionally active to suppress effector T cells.
Conclusion
The presence of IT Breg cells was an important biomarker for NIU remission. In EAU, B10 cells were the only Breg being detected within the eye at peak disease of EAU. The B10 Bregs mediate an immunoregulatory role through IL-10 production and disease severity. EAU model reflected the immunoregulatory roles of immature B cells and B10 Breg cell compositions in man. Our study indicated that subsets Bregs may have species-specific differential roles and that personalized medication with B-cell-directed inhibition may be of therapeutic potential in uveitis.
Conflict of interest
No
Authors 1
Last name
CHEN
Initials of first name(s)
YH
Department
UCL Institute of Ophthalmology, University College London
City
London
Country
United Kingdom
Authors 2
Last name
Calder
Initials of first name(s)
V
Department
UCL Institute of Ophthalmology, University College London
City
London
Country
United Kingdom
Authors 3
Last name
Lightman
Initials of first name(s)
Sue
Department
UCL Institute of Ophthalmology, University College London
City
London
Country
United Kingdom
Authors 4
Last name
Eskandarpour
Initials of first name(s)
M
Department
UCL Institute of Ophthalmology, University College London
City
London
Country
United Kingdom
Authors 5
Last name
Zhang
Initials of first name(s)
XZ
Department
UCL Institute of Ophthalmology, University College London
City
London
Country
United Kingdom
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