A role for TSLP in the development of inflammation in an asthma model.
Thymic stromal lymphopoietin (TSLP) is a cytokine that promotes CD4+ T cell homeostasis. We now demonstrate that TSLP is required to mount a normal CD4+ T cell-mediated inflammatory response. TSLP acts directly on naive, but not, memory CD4+ T cells, and promotes their proliferation in response to antigen. In addition, TSLP exerts an effect indirectly through DCs to promote Th2 differentiation of CD4+ T cells. Correspondingly, TSLP receptor (TSLPR) knockout (KO) mice exhibit strong Th1 responses, with high levels of interleukin (IL)-12, interferon-gamma, and immunoglobulin (Ig) G2a, but low production of IL-4, -5, -10, -13, and IgE; moreover, CD4+ T cells from these animals proliferate less well in response to antigen. Furthermore, TSLPR KO mice fail to develop an inflammatory lung response to inhaled antigen unless supplemented with wild-type CD4+ T cells. This underscores an important role for this cytokine in the development of inflammatory and/or allergic responses in vivo.
Al-Shami
Amin
A
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Spolski
Rosanne
R
Kelly
John
J
Keane-Myers
Andrea
A
Leonard
Warren J
WJ
D000818:Animals; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D003713:Dendritic Cells / Q000378:metabolism; D004195:Disease Models, Animal; D007136:Immunoglobulins; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D007136:Immunoglobulins; D018121:Receptors, Cytokine; C410591:Tslpr protein, mouse; D007371:Interferon-gamma; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse