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Publication : Thymic stromal lymphopoietin drives the development of IL-13<sup>+</sup> Th2 cells.

First Author  Ochiai S Year  2018
Journal  Proc Natl Acad Sci U S A Volume  115
Issue  5 Pages  1033-1038
PubMed ID  29339496 Mgi Jnum  J:257761
Mgi Id  MGI:6115393 Doi  10.1073/pnas.1714348115
Citation  Ochiai S, et al. (2018) Thymic stromal lymphopoietin drives the development of IL-13(+) Th2 cells. Proc Natl Acad Sci U S A 115(5):1033-1038
abstractText  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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