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Group 2 innate lymphoid cells express functional NKp30 receptor inducing type 2 cytokine production

Abstract:
Group 2 innate lymphoid cells (ILC2) are important in effector functions for eliciting allergic inflammation, parasite defense, epithelial repair, and lipid homeostasis. ILC2 lack rearranged Ag-specific receptors, and although many soluble factors such as cytokines and lipid mediators can influence ILC2, direct interaction of these cells with the microenvironment and other cells has been less explored. Natural cytotoxicity receptors are expressed by subsets of group 1 ILC and group 3 ILC and thought to be important for their effector function, but they have not been shown to be expressed by ILC2. Therefore, we sought to investigate the expression and functional properties of the natural cytotoxicity receptor NKp30 on human ILC2. A subset of ex vivo and cultured ILC2 express NKp30 that upon interaction with its cognate activatory ligand B7-H6 induces rapid production of type 2 cytokines. This interaction can be blocked by NKp30 blocking Ab and an inhibitory ligand, galectin-3. Higher expression of B7-H6 was observed in lesional skin biopsies of patients with atopic dermatitis, and incubation of keratinocytes with proinflammatory and type 2 cytokines upregulated B7-H6, leading to increased ILC2 cytokine production. NKp30–B7-H6 interaction is a novel cell contact mechanism that mediates activation of ILC2 and identifies a potential target for the development of novel therapeutics for atopic dermatitis and other atopic diseases.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.4049/jimmunol.1501102

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
Weatherall Insti. of Molecular Medicine
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
NDM Experimental Medicine
Role:
Author


Publisher:
American Association of Immunologists
Journal:
Journal of Immunology More from this journal
Volume:
196
Issue:
1
Pages:
45-54
Publication date:
2015-12-18
Acceptance date:
2015-10-20
DOI:
EISSN:
1550-6606
ISSN:
0022-1767


Language:
English
Keywords:
UUID:
uuid:93f07220-b483-4a5a-b361-86267dbf8a69
Deposit date:
2015-11-05

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