Thymic stromal lymphopoietin drives the development of IL-13 ⁺ Th2 cells

Abstract

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^lowPD1^low and expressed low levels of <i>Bcl6</i> and <i>Il21</i> transcripts and high levels of <i>Gata3</i>, <i>Il3</i>, and <i>Il5</i> 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.