Group 2 innate lymphoid cells are elevated and activated in chronic rhinosinusitis with nasal polyps

Julie A. Poposki, Aiko I. Klingler, Bruce Kuang-Huay Tan, Pejman Soroosh, Homayon Banie, Gavin Lewis, Kathryn E Hulse, Whitney Stevens, Anju Tripathi Peters, Leslie C Grammer III, Robert P Schleimer, Kevin Christian Welch, Stephanie Shintani Smith, David B Conley Jr, Joseph R. Raviv, James G. Karras, Omid Akbari, Robert C Kern, Atsushi Kato*

*Corresponding author for this work

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is characterized by type 2 inflammation with high levels of Th2 cytokines. Although T helper cytokines are released from T cells, innate lymphoid cells (ILC) are also known to produce high levels of the same cytokines.However, the presence of various types of ILC in CRS is poorly understood. Objective: The objective of this study was to fully characterize the presence of all ILC subsets in CRS and to identify phenotypical differences of group 2 ILC (ILC2) in CRSwNP compared to ILC2 from non-type 2 inflamed areas. Methods: We investigated the presence of ILC subsets in peripheral blood mononuclear cells (PBMC) from healthy subjects, tonsil tissue, ethmoid tissue from control subjects and patients with non-polypoid CRS (CRSsNP) and CRSwNP, as well as nasal polyp (NP) tissue from CRSwNP by flow cytometry. Sorted ILC2 were cultured in the presence and absence of IL-33 and production of IL-5 and IL-13 was assessed by Luminex. Results: We found that all ILC subsets were present in NP but ILC2 were dominant and significantly elevated compared to PBMC, tonsil, CRSsNP, and normal sinus tissue. We also found that inducible T-cell co-stimulator (ICOS) and side scatter were increased and CD127 was down-regulated in ILC2 from NP compared to blood or tonsil ILC2. Thymic stromal lymphopoietin, IL-7, and IL-33 were able to down-regulate expression of CD127 and increase side scatter in blood ILC2. Furthermore, sorted NP ILC2 but not blood ILC2 spontaneously released type 2 cytokines including IL-5 and IL-13. Conclusions and Clinical Relevance: These results suggest that ILC2 are not only elevated but also activated in CRSwNP in vivo and that ILC2 may play important roles in the type 2 inflammation in CRSwNP.

Original languageEnglish (US)
Pages (from-to)233-243
Number of pages11
JournalImmunity Inflammation and Disease
Volume5
Issue number3
DOIs
StatePublished - Jan 1 2017

Fingerprint

Nasal Polyps
Lymphocytes
Palatine Tonsil
Cytokines
Interleukin-13
Interleukin-5
Blood Cells
Inducible T-Cell Co-Stimulator Protein
Inflammation
Interleukin-7
Healthy Volunteers
Flow Cytometry
Down-Regulation
T-Lymphocytes

Keywords

  • Chronic rhinosinusitis
  • ILC2
  • Innate lymphoid cells
  • Nasal polyp
  • Type 2 inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

@article{4dae36d87bfe44a08a8d40355f6d21b6,
title = "Group 2 innate lymphoid cells are elevated and activated in chronic rhinosinusitis with nasal polyps",
abstract = "Background: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is characterized by type 2 inflammation with high levels of Th2 cytokines. Although T helper cytokines are released from T cells, innate lymphoid cells (ILC) are also known to produce high levels of the same cytokines.However, the presence of various types of ILC in CRS is poorly understood. Objective: The objective of this study was to fully characterize the presence of all ILC subsets in CRS and to identify phenotypical differences of group 2 ILC (ILC2) in CRSwNP compared to ILC2 from non-type 2 inflamed areas. Methods: We investigated the presence of ILC subsets in peripheral blood mononuclear cells (PBMC) from healthy subjects, tonsil tissue, ethmoid tissue from control subjects and patients with non-polypoid CRS (CRSsNP) and CRSwNP, as well as nasal polyp (NP) tissue from CRSwNP by flow cytometry. Sorted ILC2 were cultured in the presence and absence of IL-33 and production of IL-5 and IL-13 was assessed by Luminex. Results: We found that all ILC subsets were present in NP but ILC2 were dominant and significantly elevated compared to PBMC, tonsil, CRSsNP, and normal sinus tissue. We also found that inducible T-cell co-stimulator (ICOS) and side scatter were increased and CD127 was down-regulated in ILC2 from NP compared to blood or tonsil ILC2. Thymic stromal lymphopoietin, IL-7, and IL-33 were able to down-regulate expression of CD127 and increase side scatter in blood ILC2. Furthermore, sorted NP ILC2 but not blood ILC2 spontaneously released type 2 cytokines including IL-5 and IL-13. Conclusions and Clinical Relevance: These results suggest that ILC2 are not only elevated but also activated in CRSwNP in vivo and that ILC2 may play important roles in the type 2 inflammation in CRSwNP.",
keywords = "Chronic rhinosinusitis, ILC2, Innate lymphoid cells, Nasal polyp, Type 2 inflammation",
author = "Poposki, {Julie A.} and Klingler, {Aiko I.} and Tan, {Bruce Kuang-Huay} and Pejman Soroosh and Homayon Banie and Gavin Lewis and Hulse, {Kathryn E} and Whitney Stevens and Peters, {Anju Tripathi} and {Grammer III}, {Leslie C} and Schleimer, {Robert P} and Welch, {Kevin Christian} and Smith, {Stephanie Shintani} and {Conley Jr}, {David B} and Raviv, {Joseph R.} and Karras, {James G.} and Omid Akbari and Kern, {Robert C} and Atsushi Kato",
year = "2017",
month = "1",
day = "1",
doi = "10.1002/iid3.161",
language = "English (US)",
volume = "5",
pages = "233--243",
journal = "Immunity, inflammation and disease",
issn = "2050-4527",
publisher = "John Wiley and Sons Ltd",
number = "3",

}

TY - JOUR

T1 - Group 2 innate lymphoid cells are elevated and activated in chronic rhinosinusitis with nasal polyps

AU - Poposki, Julie A.

AU - Klingler, Aiko I.

AU - Tan, Bruce Kuang-Huay

AU - Soroosh, Pejman

AU - Banie, Homayon

AU - Lewis, Gavin

AU - Hulse, Kathryn E

AU - Stevens, Whitney

AU - Peters, Anju Tripathi

AU - Grammer III, Leslie C

AU - Schleimer, Robert P

AU - Welch, Kevin Christian

AU - Smith, Stephanie Shintani

AU - Conley Jr, David B

AU - Raviv, Joseph R.

AU - Karras, James G.

AU - Akbari, Omid

AU - Kern, Robert C

AU - Kato, Atsushi

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is characterized by type 2 inflammation with high levels of Th2 cytokines. Although T helper cytokines are released from T cells, innate lymphoid cells (ILC) are also known to produce high levels of the same cytokines.However, the presence of various types of ILC in CRS is poorly understood. Objective: The objective of this study was to fully characterize the presence of all ILC subsets in CRS and to identify phenotypical differences of group 2 ILC (ILC2) in CRSwNP compared to ILC2 from non-type 2 inflamed areas. Methods: We investigated the presence of ILC subsets in peripheral blood mononuclear cells (PBMC) from healthy subjects, tonsil tissue, ethmoid tissue from control subjects and patients with non-polypoid CRS (CRSsNP) and CRSwNP, as well as nasal polyp (NP) tissue from CRSwNP by flow cytometry. Sorted ILC2 were cultured in the presence and absence of IL-33 and production of IL-5 and IL-13 was assessed by Luminex. Results: We found that all ILC subsets were present in NP but ILC2 were dominant and significantly elevated compared to PBMC, tonsil, CRSsNP, and normal sinus tissue. We also found that inducible T-cell co-stimulator (ICOS) and side scatter were increased and CD127 was down-regulated in ILC2 from NP compared to blood or tonsil ILC2. Thymic stromal lymphopoietin, IL-7, and IL-33 were able to down-regulate expression of CD127 and increase side scatter in blood ILC2. Furthermore, sorted NP ILC2 but not blood ILC2 spontaneously released type 2 cytokines including IL-5 and IL-13. Conclusions and Clinical Relevance: These results suggest that ILC2 are not only elevated but also activated in CRSwNP in vivo and that ILC2 may play important roles in the type 2 inflammation in CRSwNP.

AB - Background: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is characterized by type 2 inflammation with high levels of Th2 cytokines. Although T helper cytokines are released from T cells, innate lymphoid cells (ILC) are also known to produce high levels of the same cytokines.However, the presence of various types of ILC in CRS is poorly understood. Objective: The objective of this study was to fully characterize the presence of all ILC subsets in CRS and to identify phenotypical differences of group 2 ILC (ILC2) in CRSwNP compared to ILC2 from non-type 2 inflamed areas. Methods: We investigated the presence of ILC subsets in peripheral blood mononuclear cells (PBMC) from healthy subjects, tonsil tissue, ethmoid tissue from control subjects and patients with non-polypoid CRS (CRSsNP) and CRSwNP, as well as nasal polyp (NP) tissue from CRSwNP by flow cytometry. Sorted ILC2 were cultured in the presence and absence of IL-33 and production of IL-5 and IL-13 was assessed by Luminex. Results: We found that all ILC subsets were present in NP but ILC2 were dominant and significantly elevated compared to PBMC, tonsil, CRSsNP, and normal sinus tissue. We also found that inducible T-cell co-stimulator (ICOS) and side scatter were increased and CD127 was down-regulated in ILC2 from NP compared to blood or tonsil ILC2. Thymic stromal lymphopoietin, IL-7, and IL-33 were able to down-regulate expression of CD127 and increase side scatter in blood ILC2. Furthermore, sorted NP ILC2 but not blood ILC2 spontaneously released type 2 cytokines including IL-5 and IL-13. Conclusions and Clinical Relevance: These results suggest that ILC2 are not only elevated but also activated in CRSwNP in vivo and that ILC2 may play important roles in the type 2 inflammation in CRSwNP.

KW - Chronic rhinosinusitis

KW - ILC2

KW - Innate lymphoid cells

KW - Nasal polyp

KW - Type 2 inflammation

UR - http://www.scopus.com/inward/record.url?scp=85029592980&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029592980&partnerID=8YFLogxK

U2 - 10.1002/iid3.161

DO - 10.1002/iid3.161

M3 - Article

VL - 5

SP - 233

EP - 243

JO - Immunity, inflammation and disease

JF - Immunity, inflammation and disease

SN - 2050-4527

IS - 3

ER -