ICOS:ICOS-ligand interaction is required for type 2 innate lymphoid cell function, homeostasis, and induction of airway hyperreactivity

Hadi Maazi; Nisheel Patel; Ishwarya Sankaranarayanan; Yuzo Suzuki; Diamanda Rigas; Pejman Soroosh; Gordon J Freeman; Arlene H Sharpe; Omid Akbari

doi:10.1016/j.immuni.2015.02.007

ICOS:ICOS-ligand interaction is required for type 2 innate lymphoid cell function, homeostasis, and induction of airway hyperreactivity

Immunity. 2015 Mar 17;42(3):538-51. doi: 10.1016/j.immuni.2015.02.007. Epub 2015 Mar 10.

Authors

Hadi Maazi¹, Nisheel Patel¹, Ishwarya Sankaranarayanan¹, Yuzo Suzuki¹, Diamanda Rigas¹, Pejman Soroosh², Gordon J Freeman³, Arlene H Sharpe⁴, Omid Akbari⁵

Affiliations

¹ Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles, California 90033, USA.
² Janssen Research and Development, San Diego, California 92121, USA.
³ Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
⁴ Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
⁵ Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles, California 90033, USA. Electronic address: akbari@usc.edu.

Abstract

Allergic asthma is caused by Th2-cell-type cytokines in response to allergen exposure. Type 2 innate lymphoid cells (ILC2s) are a newly identified subset of immune cells that, along with Th2 cells, contribute to the pathogenesis of asthma by producing copious amounts of IL-5 and IL-13, which cause eosinophilia and airway hyperreactivity (AHR), a cardinal feature of asthma. ILC2s express ICOS, a T cell costimulatory molecule with a currently unknown function. Here we showed that a lack of ICOS on murine ILC2s and blocking the ICOS:ICOS-ligand interaction in human ILC2s reduced AHR and lung inflammation. ILC2s expressed both ICOS and ICOS-ligand, and the ICOS:ICOS-ligand interaction promoted cytokine production and survival in ILC2s through STAT5 signaling. Thus, ICOS:ICOS-ligand signaling pathway is critically involved in ILC2 function and homeostasis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Asthma / genetics
Asthma / immunology*
Asthma / pathology
Female
Gene Expression Regulation
Homeostasis
Humans
Immunity, Innate
Inducible T-Cell Co-Stimulator Ligand / genetics
Inducible T-Cell Co-Stimulator Ligand / immunology*
Inducible T-Cell Co-Stimulator Protein / genetics
Inducible T-Cell Co-Stimulator Protein / immunology*
Interleukin-13 / genetics
Interleukin-13 / immunology
Interleukin-2 / genetics
Interleukin-2 / immunology
Interleukin-33
Interleukin-5 / genetics
Interleukin-5 / immunology
Interleukins / genetics
Interleukins / immunology
Lymphocytes / immunology*
Lymphocytes / pathology
Mice, Transgenic
Respiratory System / immunology
Respiratory System / pathology
STAT5 Transcription Factor / genetics
STAT5 Transcription Factor / immunology
Signal Transduction

Substances

ICOS protein, human
ICOSLG protein, human
Icos protein, mouse
Icosl protein, mouse
Il33 protein, mouse
Inducible T-Cell Co-Stimulator Ligand
Inducible T-Cell Co-Stimulator Protein
Interleukin-13
Interleukin-2
Interleukin-33
Interleukin-5
Interleukins
STAT5 Transcription Factor

Abstract

Publication types

MeSH terms

Substances

Grants and funding