Lung natural helper cells are a critical source of Th2 cell-type cytokines in protease allergen-induced airway inflammation.

By T. Halim, Ramona H Krauss, A. Sun, F. Takei. Immunity, 2012

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Overproduction of cytokines by T helper 2 (Th2) cells in the lung is thought to be a cause of asthma. Here we report that innate lymphocytes termed lung natural helper (LNH) cells are a T cell-independent source of Th2 cell-type cytokines in protease allergen-treated lungs. LNH (Lin(-)Sca-1(+)c-kit(+/lo)CD25(+)CD127(+)) cells, when stimulated by IL-33 plus IL-2, IL-7, or thymic stroma lymphopoietin (TSLP), produced large amounts of IL-5 and IL-13. Intranasal administration of protease allergen papain induced eosinophil infiltration and mucus hyperproduction in the lung of wild-type and Rag1(-/-) mice, but not in Rag2(-/-)Il2rg(-/-) mice that lack LNH cells. LNH cell depletion inhibited papain-induced airway inflammation in Rag1(-/-) mice whereas adoptive transfer of LNH cells enabled Rag2(-/-)Il2rg(-/-) mice to respond to papain. Treatment of lung explants with papain induced IL-33 and TSLP production by stroma cells and IL-5 and IL-13 production by LNH cells. Thus, LNH cells are critical for protease allergen-induced airway inflammation.

Subfields: Immunology, Physiology, Surgery

View Paper: https://www.semanticscholar.org/paper/9df4b5c2374aa3f90eee6319b30938e3084764aa

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Citations in the corpus

MHCII-Mediated Dialog between Group 2 Innate Lymphoid Cells and CD4+ T Cells Potentiates Type 2 Immunity and Promotes Parasitic Helminth Expulsion (2014, background): “In addition to antihelminthic immunity, ILC2s have also been implicated in promoting detrimental type-2 immune responses in mouse models of asthma (Barlow et al., 2012; Chang et al., 2011; Monticelli et al., 2011) and allergies (Bartemes et al., 2012; Halim et al., 2012; Salimi et al., 2013).”
TSLP elicits IL-33–independent innate lymphoid cell responses to promote skin inflammation (2013, methodology): “Depletion of ILCs attenuates AD-like dermatitis in mice To test the functional role of group2 ILCs inAD-like inflammation, we used an anti-CD25monoclonal antibody (mAb) to deplete ILCs inmice lackingT andB cells (24).”
Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages (2013, background): “3 d), and these cytokines increased further with the ad dition of IL2 or IL7, similar to results reported by ILC2s from other tissues (Moro et al., 2010; Halim et al., 2012).”
Group 2 Innate Lymphoid Cells Are Critical for the Initiation of Adaptive T Helper 2 Cell-Mediated Allergic Lung Inflammation (2014, methodology): “Naïve WT lung ILC2 gene expression (Halim et al, 2012a) was compared to publicly available (ImmGen) gene expression microarray datasets of mature myeloid and lymphoid lineages.”
The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells. (2012, positive): “Moreover, these ILCs can mediate type 2 disease as shown in several mouse asthma models (Barlow et al., 2012; Bartemes et al., 2012; Halim et al., 2012; Kim et al., 2012; Wolterink 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”