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Immunotherapy for Upper Airway Disease Generates IL-10-Producing KLRG1 + ILC2s that are Associated with Clinical Benefit

53 Pages Posted: 11 Jun 2020 Publication Status: Review Complete

See all articles by Korneliusz Golebski

Korneliusz Golebski

University of Amsterdam - Department of Experimental Immunology

Janice A. Layhadi

Imperial College London - Immunomodulation and Tolerance Group

Umit Sahiner

Imperial College London - Immunomodulation and Tolerance Group

Esther H. Steveling-Klein

Imperial College London - Immunomodulation and Tolerance Group

Madison M. Lenormand

Imperial College London - Immunomodulation and Tolerance Group

Rachael C. Y. Li

Imperial College London - Immunomodulation and Tolerance Group

Suzanne M. Bal

University of Amsterdam - Department of Experimental Immunology

Balthasar Heesters

University of Amsterdam - Department of Experimental Immunology

Gemma Vilà-Nadal

Imperial College London - Immunomodulation and Tolerance Group

Oleksandra Fedina

Imperial College London - Immunomodulation and Tolerance Group

Mongkol Lao-Araya

Imperial College London - Immunomodulation and Tolerance Group

Susanne J. H. Vijverberg

University of Amsterdam - Department of Respiratory Medicine

Anke-Hilse Maitland-van der Zee

University of Amsterdam - Department of Respiratory Medicine

Cornelis M. van Drunen

University of Amsterdam - Department of Otorhinolaryngology

Wytske J. Fokkens

University of Amsterdam - Department of Otorhinolaryngology

Stephen R. Durham

University of Amsterdam - Department of Experimental Immunology

Hergen Spits

University of Amsterdam - Department of Experimental Immunology

Mohamed Shamji

Imperial College London - Immunomodulation and Tolerance Group

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Abstract

SummaryIn this study, we addressed the role of IL-10-producing ILCs in controlling grass pollen allergy. IL-10+ ILCs are comprised in KLRG1+ILC2-lineage cells and absent on CRTH2+ ILC2 which lack KLRG1.  We observed that ILC2s in healthy subjects and grass pollen allergic patients show differential gene expression profiles. A cross-sectional study demonstrates that IL-10-producing KLRG1+ ILC2s are strongly reduced in patients with grass pollen and house dust mite allergy when compared to healthy subjects and those who have received grass pollen subcutaneous immunotherapy treatment. In a prospective double-blind, placebo-controlled trial of grass pollen sublingual immunotherapy (SLIT), we observed that the capacity of ILC2 to produce IL-10 was restored in patients who received SLIT, but not patients receiving a placebo. Finally, we demonstrated that these IL-10-producing ILCs are functional and play a crucial role in restoring barrier function and tissue balance in allergic diseases.

Keywords: innate lymphoid cells, epithelial barrier, allergic rhinitis, allergen immunotherapy

Suggested Citation

Golebski, Korneliusz and Layhadi, Janice A. and Sahiner, Umit and Steveling-Klein, Esther H. and Lenormand, Madison M. and Li, Rachael C. Y. and Bal, Suzanne M. and Heesters, Balthasar and Vilà-Nadal, Gemma and Fedina, Oleksandra and Lao-Araya, Mongkol and Vijverberg, Susanne J. H. and Maitland-van der Zee, Anke-Hilse and van Drunen, Cornelis M. and Fokkens, Wytske J. and Durham, Stephen R. and Spits, Hergen and Shamji, Mohamed, Immunotherapy for Upper Airway Disease Generates IL-10-Producing KLRG1 + ILC2s that are Associated with Clinical Benefit. Available at SSRN: https://ssrn.com/abstract=3611048 or http://dx.doi.org/10.2139/ssrn.3611048
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Korneliusz Golebski

University of Amsterdam - Department of Experimental Immunology ( email )

Spui 21
Amsterdam, 1018 WB
Netherlands

Janice A. Layhadi

Imperial College London - Immunomodulation and Tolerance Group ( email )

United Kingdom

Umit Sahiner

Imperial College London - Immunomodulation and Tolerance Group ( email )

United Kingdom

Esther H. Steveling-Klein

Imperial College London - Immunomodulation and Tolerance Group ( email )

United Kingdom

Madison M. Lenormand

Imperial College London - Immunomodulation and Tolerance Group ( email )

United Kingdom

Rachael C. Y. Li

Imperial College London - Immunomodulation and Tolerance Group ( email )

United Kingdom

Suzanne M. Bal

University of Amsterdam - Department of Experimental Immunology ( email )

Spui 21
Amsterdam, 1018 WB
Netherlands

Balthasar Heesters

University of Amsterdam - Department of Experimental Immunology ( email )

Spui 21
Amsterdam, 1018 WB
Netherlands

Gemma Vilà-Nadal

Imperial College London - Immunomodulation and Tolerance Group ( email )

United Kingdom

Oleksandra Fedina

Imperial College London - Immunomodulation and Tolerance Group ( email )

United Kingdom

Mongkol Lao-Araya

Imperial College London - Immunomodulation and Tolerance Group ( email )

United Kingdom

Susanne J. H. Vijverberg

University of Amsterdam - Department of Respiratory Medicine ( email )

Amsterdam
Netherlands

Anke-Hilse Maitland-van der Zee

University of Amsterdam - Department of Respiratory Medicine ( email )

Amsterdam
Netherlands

Cornelis M. Van Drunen

University of Amsterdam - Department of Otorhinolaryngology ( email )

Spui 21
Amsterdam, 1018 WB
Netherlands

Wytske J. Fokkens

University of Amsterdam - Department of Otorhinolaryngology ( email )

Spui 21
Amsterdam, 1018 WB
Netherlands

Stephen R. Durham

University of Amsterdam - Department of Experimental Immunology ( email )

Spui 21
Amsterdam, 1018 WB
Netherlands

Hergen Spits

University of Amsterdam - Department of Experimental Immunology ( email )

Amsterdam
Netherlands

Mohamed Shamji (Contact Author)

Imperial College London - Immunomodulation and Tolerance Group ( email )

United Kingdom

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