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Publication : Thymic stromal lymphopoietin (TSLP)-induced polyclonal B-cell activation and autoimmunity are mediated by CD4+ T cells and IL-4.

First Author  Iseki M Year  2012
Journal  Int Immunol Volume  24
Issue  3 Pages  183-95
PubMed ID  22281511 Mgi Jnum  J:182756
Mgi Id  MGI:5316546 Doi  10.1093/intimm/dxr113
Citation  Iseki M, et al. (2012) Thymic stromal lymphopoietin (TSLP)-induced polyclonal B-cell activation and autoimmunity are mediated by CD4+ T cells and IL-4. Int Immunol 24(3):183-95
abstractText  The cytokine thymic stromal lymphopoietin (TSLP) functions as a regulator of bone marrow B-cell development and a key initiator of allergic inflammation. In the current study, we show that mature B cells, derived from transgenic mice with systemically elevated levels of TSLP (K5-TSLP mice), exhibit markedly enhanced mitogenic responses in vitro and that this enhanced responsiveness leads to polyclonal B-cell activation and development of autoimmune hemolytic anemia in vivo. In contrast, B cells derived from K5-TSLP mice lacking CD4(+) T cells failed to show polyclonal activation. Furthermore, neither mature B-cell activation nor hemolytic anemia occurred in IL-4-deficient K5-TSLP mice. Consistent with these findings, activation of mature B cells occurred independently of B-cell intrinsic TSLP signals. Taken together, our results demonstrate that systemic alterations in TSLP, through induction of IL-4 from CD4(+) T cells and other cell types, functions as an important factor in peripheral B-cell homeostasis and promotion of humoral autoimmunity.
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