T-bet controls severity of hypersensitivity pneumonitis

Hossam Aly Abdelsamed, Meena Desai, Stephanie C. Nance, Elizabeth Fitzpatrick

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Hypersensitivity Pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled environmental antigens. The disease is characterized by alveolitis, granuloma formation and in some patients' fibrosis. IFN plays a critical role in HP; in the absence of IFN granuloma formation does not occur. However, recent studies using animal models of HP have suggested that HP is a Th17 disease calling into question the role of IFN. In this study, we report that initially IFN production is dependent on IL-18 and the transcription factor T-bet, however as the disease continues IFN production is IL-18-independent and partially T-bet dependent. Although IFN production is required for granuloma formation its role is distinct from that of T-bet. Mice that are deficient in T-bet and exposed to S. rectivirgula develop more severe disease characterized by an exacerbated Th17 cell response, decreased Th1 cell response, and increased collagen production in the lung. T-bet-mediated protection does not appear to be due to the development of a protective Th1 response; shifting the balance from a Th17 predominant response to a Th1 response by inhibition of IL-6 also results in lung pathology. The results from this study suggest that both Th1 and Th17 cells can be pathogenic in this model and that IFN and T-bet play divergent roles in the disease process.

Original languageEnglish (US)
Article number15
JournalJournal of Inflammation
Volume8
DOIs
StatePublished - Jun 27 2011

Fingerprint

Extrinsic Allergic Alveolitis
Granuloma
Th17 Cells
Th1 Cells
Interleukin-18
Lung
Pulmonary diseases
Interstitial Lung Diseases
Pathology
Interleukin-6
Animals
Fibrosis
Collagen
Animal Models
Antigens

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Cell Biology

Cite this

T-bet controls severity of hypersensitivity pneumonitis. / Abdelsamed, Hossam Aly; Desai, Meena; Nance, Stephanie C.; Fitzpatrick, Elizabeth.

In: Journal of Inflammation, Vol. 8, 15, 27.06.2011.

Research output: Contribution to journalArticle

Abdelsamed, Hossam Aly ; Desai, Meena ; Nance, Stephanie C. ; Fitzpatrick, Elizabeth. / T-bet controls severity of hypersensitivity pneumonitis. In: Journal of Inflammation. 2011 ; Vol. 8.
@article{b2e993c25774474e8bd7e4686dff1566,
title = "T-bet controls severity of hypersensitivity pneumonitis",
abstract = "Hypersensitivity Pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled environmental antigens. The disease is characterized by alveolitis, granuloma formation and in some patients' fibrosis. IFN plays a critical role in HP; in the absence of IFN granuloma formation does not occur. However, recent studies using animal models of HP have suggested that HP is a Th17 disease calling into question the role of IFN. In this study, we report that initially IFN production is dependent on IL-18 and the transcription factor T-bet, however as the disease continues IFN production is IL-18-independent and partially T-bet dependent. Although IFN production is required for granuloma formation its role is distinct from that of T-bet. Mice that are deficient in T-bet and exposed to S. rectivirgula develop more severe disease characterized by an exacerbated Th17 cell response, decreased Th1 cell response, and increased collagen production in the lung. T-bet-mediated protection does not appear to be due to the development of a protective Th1 response; shifting the balance from a Th17 predominant response to a Th1 response by inhibition of IL-6 also results in lung pathology. The results from this study suggest that both Th1 and Th17 cells can be pathogenic in this model and that IFN and T-bet play divergent roles in the disease process.",
author = "Abdelsamed, {Hossam Aly} and Meena Desai and Nance, {Stephanie C.} and Elizabeth Fitzpatrick",
year = "2011",
month = "6",
day = "27",
doi = "10.1186/1476-9255-8-15",
language = "English (US)",
volume = "8",
journal = "Journal of Inflammation",
issn = "1476-9255",
publisher = "Springer Nature",

}

TY - JOUR

T1 - T-bet controls severity of hypersensitivity pneumonitis

AU - Abdelsamed, Hossam Aly

AU - Desai, Meena

AU - Nance, Stephanie C.

AU - Fitzpatrick, Elizabeth

PY - 2011/6/27

Y1 - 2011/6/27

N2 - Hypersensitivity Pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled environmental antigens. The disease is characterized by alveolitis, granuloma formation and in some patients' fibrosis. IFN plays a critical role in HP; in the absence of IFN granuloma formation does not occur. However, recent studies using animal models of HP have suggested that HP is a Th17 disease calling into question the role of IFN. In this study, we report that initially IFN production is dependent on IL-18 and the transcription factor T-bet, however as the disease continues IFN production is IL-18-independent and partially T-bet dependent. Although IFN production is required for granuloma formation its role is distinct from that of T-bet. Mice that are deficient in T-bet and exposed to S. rectivirgula develop more severe disease characterized by an exacerbated Th17 cell response, decreased Th1 cell response, and increased collagen production in the lung. T-bet-mediated protection does not appear to be due to the development of a protective Th1 response; shifting the balance from a Th17 predominant response to a Th1 response by inhibition of IL-6 also results in lung pathology. The results from this study suggest that both Th1 and Th17 cells can be pathogenic in this model and that IFN and T-bet play divergent roles in the disease process.

AB - Hypersensitivity Pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled environmental antigens. The disease is characterized by alveolitis, granuloma formation and in some patients' fibrosis. IFN plays a critical role in HP; in the absence of IFN granuloma formation does not occur. However, recent studies using animal models of HP have suggested that HP is a Th17 disease calling into question the role of IFN. In this study, we report that initially IFN production is dependent on IL-18 and the transcription factor T-bet, however as the disease continues IFN production is IL-18-independent and partially T-bet dependent. Although IFN production is required for granuloma formation its role is distinct from that of T-bet. Mice that are deficient in T-bet and exposed to S. rectivirgula develop more severe disease characterized by an exacerbated Th17 cell response, decreased Th1 cell response, and increased collagen production in the lung. T-bet-mediated protection does not appear to be due to the development of a protective Th1 response; shifting the balance from a Th17 predominant response to a Th1 response by inhibition of IL-6 also results in lung pathology. The results from this study suggest that both Th1 and Th17 cells can be pathogenic in this model and that IFN and T-bet play divergent roles in the disease process.

UR - http://www.scopus.com/inward/record.url?scp=79959439264&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959439264&partnerID=8YFLogxK

U2 - 10.1186/1476-9255-8-15

DO - 10.1186/1476-9255-8-15

M3 - Article

VL - 8

JO - Journal of Inflammation

JF - Journal of Inflammation

SN - 1476-9255

M1 - 15

ER -