期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 5, 页码 1033-1038出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1714348115
关键词
TSLP; Th2 cells; effector T cells; IL-13; IL-4
资金
- Independent Research Organization from Health Research Council of New Zealand
- Marjorie Barclay Trust
- French Ministere de l'Enseignement Superieur et de la Recherche
- Betty Coker PhD scholarship
- National Institute of Allergy and Infectious Diseases, NIH
T helper 2 (Th2) cells are pivotal in the development of allergy. Allergen exposure primes IL-4(+) Th2 cells in lymph node, but production of effector cytokines including IL-5 and IL-13 is thought to require additional signals from antigen and the environment. Here we report that a substantial proportion of naive CD4(+) T cells in spleen and lymph node express receptors for the epithelium-derived inflammatory cytokine thymic stromal lymphopoietin (TSLP). Culture of naive CD4(+) T cells in anti-(a) CD3, aCD28, and TSLP-supplemented Th2 conditions enabled the development of a unique population of IL-13-single positive (IL-13-SP) CD4(+) T cells; TSLP and Th2 conditions were both required for their development. Sorting experiments revealed that IL-13-SP Th2 cells originated from IL-4-negative precursors and coexpressed transcripts for the Th2 cytokines IL-5 and IL-9. In vivo, high TSLP levels acted directly on CD4(+) T cells to induce the development of IL-13-SP and IL-4(+) IL-13(+) double-positive populations in lymph node. These cells were phenotypically similar to Th2 effector cells and were CXCR5(low)PD1(low) and expressed low levels of Bcl6 and Il21 transcripts and high levels of Gata3, Il3, and Il5. Our findings suggest a role of TSLP in directly promoting Th2 cell effector function and support the notion of TSLP as a key driver of Th2 inflammation.
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