title: Thymic stromal lymphopoietin (TSLP)-induced polyclonal B-cell activation and autoimmunity are mediated by CD4+ T cells and IL-4.
abstract: 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.
authors.affiliation: Benaroya Research Institute, Seattle, WA 98101, USA.
authors.forename: Masanori
authors.initials: M
authors.lastname: Iseki
authors.forename: Miyuki
authors.initials: M
authors.lastname: Omori-Miyake
authors.forename: Whitney
authors.initials: W
authors.lastname: Xu
authors.forename: Xiaocui
authors.initials: X
authors.lastname: Sun
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takaki
authors.forename: David J
authors.initials: DJ
authors.lastname: Rawlings
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
mesh_terms: D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology; D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015847:Interleukin-4 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D015847:Interleukin-4; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse