- Authors:
-
Scapini, Patrizia; 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
- Language:
-
Inglese
- Referee:
-
Sì
- 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
- 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:
-
February 21, 2014
- Last Modified:
-
November 27, 2022
- Bibliographic citation:
-
Scapini, Patrizia; 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.
41
,
2011
,
pp. E823-E832
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