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

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

*Corresponding author for this work

Research output: Contribution to journalArticle

36 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 K.} and Pejman Soroosh and Homayon Banie and Gavin Lewis and Hulse, {Kathryn E.} and Stevens, {Whitney W.} and Peters, {Anju T.} and Grammer, {Leslie C.} and Schleimer, {Robert P.} and Welch, {Kevin C.} and Smith, {Stephanie S.} and Conley, {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",

}

Group 2 innate lymphoid cells are elevated and activated in chronic rhinosinusitis with nasal polyps. / Poposki, Julie A.; Klingler, Aiko I.; Tan, Bruce K.; Soroosh, Pejman; Banie, Homayon; Lewis, Gavin; Hulse, Kathryn E.; Stevens, Whitney W.; Peters, Anju T.; Grammer, Leslie C.; Schleimer, Robert P.; Welch, Kevin C.; Smith, Stephanie S.; Conley, David B.; Raviv, Joseph R.; Karras, James G.; Akbari, Omid; Kern, Robert C.; Kato, Atsushi.

In: Immunity Inflammation and Disease, Vol. 5, No. 3, 01.01.2017, p. 233-243.

Research output: Contribution to journalArticle

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 K.

AU - Soroosh, Pejman

AU - Banie, Homayon

AU - Lewis, Gavin

AU - Hulse, Kathryn E.

AU - Stevens, Whitney W.

AU - Peters, Anju T.

AU - Grammer, Leslie C.

AU - Schleimer, Robert P.

AU - Welch, Kevin C.

AU - Smith, Stephanie S.

AU - Conley, 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

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