In:
The Journal of Immunology, The American Association of Immunologists, Vol. 194, No. 1_Supplement ( 2015-05-01), p. 114.12-114.12
Kurzfassung:
The oncoprotein and transcription factor Bcl-3 (B cell leukemia-3) is a member of the IkB family of NF-κB inhibitors and was originally identified as a component of a chromosomal rearrangement in some B cell lymphomas. In contrast to other IkB proteins, Bcl-3 associates with p50 and p52 homodimers and is predominantly a nuclear protein involved in regulating nuclear NF-kB activity. To understand more about the effects of Bcl-3 on T cells, we have generated a new mouse model, where Bcl-3 is overexpressed specifically in T cells. We could show that mice overexpressing Bcl-3 solely in T cells developed spontaneous colitis accompanied by a massive cell infiltration into the colon. Interestingly, the TCRgd+ T cell population was dramatically increased in the colonic IEL population of the Bcl-3 overexpressing mice. By examing Tregs in these mice, we found that overexpression of Bcl-3 strongly impairs Treg cell function, which was accompanied by decreased expression of CD25, Foxp3 and the co-inhibitory molecule CTLA-4. Hence, the loss of suppression of Bcl-3 overexpressing Tregs might result in the development of severe spontaneous colitis. Our data emphasize a novel pathway in the maintenance of viability and suppressive function of Tregs in the gut that critically involves Bcl-3 as a negative regulator, qualifying this protein as an interesting pharmacological target for the treatment of IBD.
Materialart:
Online-Ressource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.194.Supp.114.12
Sprache:
Englisch
Verlag:
The American Association of Immunologists
Publikationsdatum:
2015
ZDB Id:
1475085-5
