Spred1, a suppressor of the ras-ERK pathway, negatively regulates expansion and function of group 2 innate lymphoid cells

Mayu Suzuki, Rimpei Morita, Yasuko Hirata, Takashi Shichita, Akihiko Yoshimura

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Cytokines from group 2 innate lymphoid cells (ILC2s) have been implicated in acute allergic responses, such as papain-induced lung inflammation. However, the means of homeostatic regulation of ILC2s have not been established. In this study, we demonstrated that Spred1, a negative regulator of the Ras-ERK pathway, plays an important role in the proliferation and apoptosis of ILC2s and in cytokine secretion from ILC2s. Intranasal administration of papain stimulated IL-5 and IL-13 production in the lung, which was enhanced when Spred1 was deleted. In vitro, Spred1<sup>-/-</sup> ILC2s proliferated faster than wild type ILC2s did and produced higher levels of cytokines in response to IL-33. On the contrary, a MEK inhibitor suppressed ILC2 proliferation and cytokine production. Spred1 deficiency resulted in stabilization of GATA3, which has been shown to play essential roles in the maintenance and cytokine production of ILC2. These data suggest that Spred1 negatively regulates ILC2 development and functions through the suppression of the Ras-ERK pathway.

Original languageEnglish
Pages (from-to)1273-1281
Number of pages9
JournalJournal of Immunology
Volume195
Issue number3
DOIs
Publication statusPublished - 2015 Aug 1

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MAP Kinase Signaling System
Lymphocytes
Cytokines
Papain
Intranasal Administration
Interleukin-13
Interleukin-5
Mitogen-Activated Protein Kinase Kinases
Pneumonia
Maintenance
Apoptosis
Lung

ASJC Scopus subject areas

  • Immunology

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Spred1, a suppressor of the ras-ERK pathway, negatively regulates expansion and function of group 2 innate lymphoid cells. / Suzuki, Mayu; Morita, Rimpei; Hirata, Yasuko; Shichita, Takashi; Yoshimura, Akihiko.

In: Journal of Immunology, Vol. 195, No. 3, 01.08.2015, p. 1273-1281.

Research output: Contribution to journalArticle

Suzuki, Mayu ; Morita, Rimpei ; Hirata, Yasuko ; Shichita, Takashi ; Yoshimura, Akihiko. / Spred1, a suppressor of the ras-ERK pathway, negatively regulates expansion and function of group 2 innate lymphoid cells. In: Journal of Immunology. 2015 ; Vol. 195, No. 3. pp. 1273-1281.
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