TSLP conditions the lung immune environment for the generation of pathogenic innate and antigen-specific adaptive immune responses

Mark B. Headley, Baohua Zhou, Weihui X. Shih, Theingi Aye, Michael R. Comeau, Steven F. Ziegler

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Thymic stromal lymphopoietin (TSLP) is crucial for the development of atopic diseases in humans and mice. Mice that express a lung-specific TSLP transgene (surfactant protein C promoter (SPC)-TSLP) develop a spontaneous and progressive asthma-like disease, suggesting that TSLP expression alone was sufficient for disease development. In this study, we show that, in fact, TSLP alone only causes a weak innate response that is insufficient for development of full airway inflammatory disease. Complete disease development requires both TSLP and antigenic stimulation. These data suggest that the spontaneous lung inflammation observed in SPC-TSLP mice reflects a TSLP-driven predisposition toward the development of aberrant responses against innocuous environmental Ags. This provides evidence that TSLP may act directly to induce susceptibility to the inappropriate allergic responses that characterize atopy and asthma. We additionally show that disease development requires CD4 T cells but not B cells. Further, we reveal a TSLP-driven innate response involving mucus overproduction and goblet cell metaplasia. Taken together, these data suggest a multifaceted model of TSLP-mediated airway inflammation, with an initial activation of resident innate immune cells, followed by activation of the adaptive immune system and full disease development. This study provides new insight into the unique features of the asthma pathology contributed by the innate and adaptive immune responses in response to TSLP stimulation.

Original languageEnglish
Pages (from-to)1641-1647
Number of pages7
JournalJournal of Immunology
Volume182
Issue number3
StatePublished - Feb 1 2009

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Adaptive Immunity
Antigens
Lung
Asthma
Protein C
Surface-Active Agents
thymic stromal lymphopoietin
Goblet Cells
Immune System Diseases
Metaplasia
Mucus
Transgenes
Innate Immunity
Pneumonia
B-Lymphocytes
Pathology
Inflammation
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

TSLP conditions the lung immune environment for the generation of pathogenic innate and antigen-specific adaptive immune responses. / Headley, Mark B.; Zhou, Baohua; Shih, Weihui X.; Aye, Theingi; Comeau, Michael R.; Ziegler, Steven F.

In: Journal of Immunology, Vol. 182, No. 3, 01.02.2009, p. 1641-1647.

Research output: Contribution to journalArticle

Headley, Mark B. ; Zhou, Baohua ; Shih, Weihui X. ; Aye, Theingi ; Comeau, Michael R. ; Ziegler, Steven F. / TSLP conditions the lung immune environment for the generation of pathogenic innate and antigen-specific adaptive immune responses. In: Journal of Immunology. 2009 ; Vol. 182, No. 3. pp. 1641-1647.
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