Journal
INTERNATIONAL IMMUNOLOGY
Volume 24, Issue 3, Pages 183-195Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxr113
Keywords
autoantibody; cytokine; hemolytic anemia; Th2
Categories
Funding
- National Institute of Health grant [AI068731, AR056113, AI044259]
- Japan Society for the Promotion of Science [21790488]
- Uehara Memorial Foundation
- Grants-in-Aid for Scientific Research [21790488, 22590446] Funding Source: KAKEN
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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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