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

Abstract

SignificanceT helper 2 (Th2) cells are defined by their ability to produce the hallmark cytokine IL-4. However, to mediate allergic inflammation in tissues, Th2 cells must secrete additional cytokines including IL-13 and IL-5. We used IL-4 and IL-13 dual-reporter mice to show that naive CD4+ T cells cultured in the presence of IL-4 and thymic stromal lymphopoietin (TSLP) generate a population of IL-4negIL-13pos Th2 cells that develop from IL-4neg precursors and express the Th2 effector cytokines IL-5 and IL-9. In vivo, high TSLP levels promote the development of a similar population of IL-4negIL-13pos T cells that also express Gata3, Il5, and Il3 transcripts. Thus, TSLP drives the early differentiation of a distinct population of effector Th2 cells with pro-inflammatory properties.

Neuroimmune interactions in chronic itch of atopic dermatitis

“…For example, mast cell proteases not only trigger pruritus via activation of PAR2 + sensory afferent neurons, 25 but also stimulate release of TSLP from keratinocytes. [45][46][47] Additional keratinocyte alarmins (e.g. TSLP binds to TSLPR on Th2 cells and type 2 innate lymphoid cells, leading to production of pruritogenic type 2 cytokines.…”

“…TSLP binds to TSLPR on Th2 cells and type 2 innate lymphoid cells, leading to production of pruritogenic type 2 cytokines. [45][46][47] Additional keratinocyte alarmins (e.g. IL-33) function similarly.…”

Shaping the diversity of Th2 cell responses in epithelial tissues and its potential for allergy treatment

“…TSLP is produced by epithelia that are exposed to different insults. Its receptor is expressed on naïve Th cells and can drive the differentiation of a distinct pro‐inflammatory murine Th2 cell population characterized by IL‐13 expression if systemic TSLP levels are sensed in lymphoid organs . TSLP has also been shown to support Th2 cell responses via suppression of IL‐12 secretion by DCs.…”

“…IL‐13 positive T cells have been identified that lack IL‐4 co‐expression. They have been shown to derive from naïve T cell precursors independently of IL‐4 producing cells in Th2 cell conditions supplemented with TSLP and constitute a separate pro‐inflammatory Th2 cell subset in a mouse model . Therefore, Th2 functionalities might arise, which are biased toward one or another signature cytokine.…”

T cells in severe childhood asthma

“…Notable examples are TSLP and IL‐33, which are elevated in the airways of severe asthmatics with worse lung function. These cytokines have each been implicated in Th2 differentiation, but may also augment Th2 effector function …”