The transcription factor GATA3 controls cell fate and maintenance of type 2 innate lymphoid cells

By T. Hoyler, Christoph S. N. Klose, A. Souabni, Adriana Turqueti‐Neves, D. Pfeifer, E. Rawlins, D. Voehringer, M. Busslinger, A. Diefenbach. Immunity, 2012

808 citations recorded by the source corpus.

Innate lymphoid cells (ILCs) reside at mucosal surfaces and control immunity to intestinal infections. Type 2 innate lymphoid cells (ILC2) produce cytokines such as IL-5 and IL-13 and are required for immune defense against helminth infections and are involved in the pathogenesis of airway hyperreactivity. Here, we have investigated the role of the transcription factor GATA3 for ILC2 differentiation and maintenance. We showed that ILC2 and their lineage-specified bone marrow precursor (ILC2P), as identified here, were characterized by continuous high expression of GATA3. Analysis of mice with temporary deletion of GATA3 in all ILCs showed that GATA3 was required for the differentiation and maintenance of ILC2 but not for RORγt+ ILCs. Thus, our data demonstrate GATA3 is essential for ILC2 fate decisions, and reveal similarities between the transcriptional programs controlling ILC and T helper cell fates.

Subfields: Immunology, Surgery

View Paper: https://www.semanticscholar.org/paper/6865f1bc18d01c6d5be61b7999cc07b6c5ee107e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. D. Artis
2. M. V. D. van den Brink
3. A. Hanash
4. J. Dudakov
5. Andrew N. J. McKenzie
6. L. Monticelli

In Surgery

1. D. Artis
2. Andrew N. J. McKenzie

Citations in the corpus

• Innate lymphoid cells and asthma. (2014, neutral): “ILC2s require the transcription factor retinoic acid receptor–related orphan receptor (ROR) a(11,12) and the GATA transcription factor Gata3.(13) ILC2s have been shown to mediate eosinophilia and goblet cell hyperplasia, both of which are critical for antihelminth responses and for allergic diseases”
• The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells. (2012, neutral): “In an accompanying paper (Hoyler et al., 2012), it is demonstrated that GATA3 is essential for the development of ILC2s and that during development of ILC2s from its progenitor, high levels of GATA3 is expressed before RORa.”
• Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages (2013, neutral): “In contrast to VAT ILC2s, bone marrow ILC2s (lineage IL7R+ T1/ST2+; Brickshawana et al., 2011), which were also described as ILC2 precursors (Hoyler et al., 2012), did not express basal IL13 as assessed with IL13 lin eage tracking (2.0 ± 0.3%, n = 8), although marrow ILC2s were predominantly IL4…”
• MHCII-Mediated Dialog between Group 2 Innate Lymphoid Cells and CD4+ T Cells Potentiates Type 2 Immunity and Promotes Parasitic Helminth Expulsion (2014, background): “The depletion of ILC2s has also been reported in mice in which Id2CreER mediated the excision of a conditional Gata3 allele (Hoyler et al., 2012); however, it is becoming clear that GATA3 is required for all ILC populations (Serafini et al., 2014).”
• Interleukin-22: immunobiology and pathology (2015, background): “In addition, GATA3 which is another factor involved at multiple stages of T cell development (113) and was originally thought to be only involved with ILC2 lineage development (101, 114, 115), also seems to play a crucial role in ILC3 differentiation (116).”
• Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages. (2014, neutral): “CD25 a4b7 + cells represented the previously identified ILC2P uniformly expressing the IL-33R (Figure 1B) (Hoyler et al., 2012).”
• TSLP elicits IL-33–independent innate lymphoid cell responses to promote skin inflammation (2013, background): “A recent report indicated that TSLP-TSLPR signaling is not required for the development of group 2 ILCs in the periphery, nor is it necessary for bone marrow–derived progenitors to differentiate into mature, resting group 2 ILCs (28).”
• Innate Lymphoid Cells: 10 Years On. (2018, neutral): “ILC2s contain larger amounts of the transcription factor GATA3 than the other ILC subsets, and absence of GATA3 inhibits the development and function of these cells (Hoyler et al., 2012; Klein Wolterink et al., 2013; Furusawa et al., 2013; Mjösberg et al., 2012).”
• A role for IL-25 and IL-33–driven type-2 innate lymphoid cells in atopic dermatitis (2013, background): “We therefore investigated whether a KLRG1–E-cadherin interaction may alter ILC2 function and act as a suppressive mechanism for dampening the ILC2 response, PMA/ ionomycin-activated human ILC2s were then cultured with recombinant plate-bound E-cadherin for 24 h. Supporting the inhibitory role of E-c”