Publications

Myeloid cells, BAFF, and IFN-gamma establish an inflammatory loop that exacerbates autoimmunity in Lyn-deficient mice  (2010)

Authors:
Scapini P; Hu Y; Chu CL; Migone TS; Defranco AL; Cassatella MA; Lowell CA
Title:
Myeloid cells, BAFF, and IFN-gamma establish an inflammatory loop that exacerbates autoimmunity in Lyn-deficient mice
Year:
2010
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:
Journal of Experimental Medicine
ISSN of journal:
0022-1007
N° Volume:
207
Number or Folder:
8
Page numbers:
1757-1773
Code PMID:
20624892
Keyword:
Autoimmunity, BAFF, IFN-{gamma}, Lyn-deficient mice
Short description of contents:
Autoimmunity is traditionally attributed to altered lymphoid cell selection and/or tolerance, whereas the contribution of innate immune cells is less well understood. Autoimmunity is also associated with increased levels of B cell-activating factor of the TNF family (BAFF; also known as B lymphocyte stimulator), a cytokine that promotes survival of self-reactive B cell clones. We describe an important role for myeloid cells in autoimmune disease progression. Using Lyn-deficient mice, we show that overproduction of BAFF by hyperactive myeloid cells contributes to inflammation and autoimmunity in part by acting directly on T cells to induce the release of IFN-gamma. Genetic deletion of IFN-gamma or reduction of BAFF activity, achieved by either reducing myeloid cell hyperproduction or by treating with an anti-BAFF monoclonal antibody, reduced disease development in lyn(-/-) mice. The increased production of IFN-gamma in lyn(-/-) mice feeds back on the myeloid cells to further stimulate BAFF release. Expression of BAFF receptor on T cells was required for their full activation and IFN-gamma release. Overall, our data suggest that the reciprocal production of BAFF and IFN-gamma establishes an inflammatory loop between myeloid cells and T cells that exacerbates autoimmunity in this model. Our findings uncover an important pathological role of BAFF in autoimmune disorders.
Product ID:
57241
Handle IRIS:
11562/344319
Deposited On:
November 9, 2016
Last Modified:
November 23, 2016
Bibliographic citation:
Scapini P; Hu Y; Chu CL; Migone TS; Defranco AL; Cassatella MA; Lowell CA, Myeloid cells, BAFF, and IFN-gamma establish an inflammatory loop that exacerbates autoimmunity in Lyn-deficient mice «Journal of Experimental Medicine» , vol. 207 , n. 82010pp. 1757-1773

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