Publications

B cell-derived IL-10 suppresses inflammatory disease in Lyn-deficient mice  (2011)

Authors:
Scapini P; Lamagna C; Hu Y; Lee K; Tang Q; Defranco AL; Lowell CA
Title:
B cell-derived IL-10 suppresses inflammatory disease in Lyn-deficient mice
Year:
2011
Type of item:
Articolo in Rivista
Tipologia ANVUR:
Articolo su rivista
Nations of authors:
STATI UNITI D'AMERICA; ITALIA
Language:
Inglese
Format:
A Stampa
Referee:
Name of journal:
Proceedings of the National Academy of Sciences of the United States of America
ISSN of journal:
0027-8424
N° Volume:
108
Number or Folder:
41
Page numbers:
E823-E832
Code PMID:
21911371
Keyword:
Lyn kinase deficient mice, autoimmune/autoinflammatory disease, B cells
Short description of contents:
Lyn kinase deficient mice represent a well established genetic model of autoimmune/autoinflammatory disease that resembles systemic lupus erythematosus. We report that IL-10 plays a crucial immunosuppressive role in this model, modulating the inflammatory component of the disease caused by myeloid and T-cell activation. Double-mutant lyn(-/-)IL-10(-/-) mice manifested severe splenomegaly and lymphadenopathy, dramatically increased proinflammatory cytokine production, and severe tissue inflammation. Single-mutant lyn(-/-)mice showed expansion of IL-10-producing B cells. Interestingly, WT B cells adoptively transferred into lyn(-/-) mice showed increased differentiation into IL-10-producing B cells that assumed a similar phenotype to endogenous lyn(-/-) IL-10-producing B cells, suggesting that the inflammatory environment present in lyn(-/-) mice induces IL-10-producing B-cell differentiation. B cells, but not T or myeloid cells, were the critical source of IL-10 able to reduce inflammation and autoimmunity in double mutant lyn(-/-)IL-10(-/-) mice. IL-10 secretion by B cells was also crucial to sustain transcription factor Forkhead Box P3 (Foxp3) expression in regulatory T cells during disease development. These data reveal a dominant immunosuppressive function of B-cell-derived IL-10 in the Lyn-deficient model of autoimmunity, extending our current understanding of the role of IL-10 and IL-10-producing B cells in systemic lupus erythematosus.
Product ID:
62840
Handle IRIS:
11562/363841
Deposited On:
November 3, 2016
Last Modified:
November 23, 2016
Bibliographic citation:
Scapini P; Lamagna C; Hu Y; Lee K; Tang Q; Defranco AL; Lowell CA, B cell-derived IL-10 suppresses inflammatory disease in Lyn-deficient mice «Proceedings of the National Academy of Sciences of the United States of America» , vol. 108 , n. 412011pp. E823-E832

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