Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13.

Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13. Research Abstract Details 

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Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13. Abstract Text:

Antonios O Aliprantis,Jingsong Wang,John W Fathman,Raphael Lemaire,David M Dorfman,Robert Lafyatis,Laurie H Glimcher,

Tissue remodeling with fibrosis is a predominant pathophysiological mechanism of many human diseases. Systemic sclerosis is a rare, often lethal, disorder of unknown etiology manifested by dermal fibrosis (scleroderma) and excessive connective tissue deposition in internal organs. Currently, there are no available antifibrotic therapeutics, a reflection of our lack of understanding of this process. Animal models of scleroderma are useful tools to dissect the transcription factors and cytokines that govern fibrosis. A disproportionate increase of type 2 cytokines, like TGF-beta and IL-4, more than type 1 cytokines, like IFN-gamma, is thought to underlie the pathogenesis of scleroderma. In this study, we show that mice deficient in the transcription factor T-box expressed in T cells (T-bet), a master regulator of type 1 immunity, display increased sensitivity to bleomycin-induced dermal sclerosis. Despite the well-established role of T-bet in adaptive immunity, we also show that RAG2(-/-) mice, which lack T and B cells, are vulnerable to bleomycin-induced scleroderma and that RAG2/T-bet double-deficient mice maintain the increased sensitivity to bleomycin observed in T-bet(-/-) mice. Furthermore, overexpression of T-bet in T cells does not affect the induction of skin sclerosis in this model. Lastly, we show that IL-13 is the profibrotic cytokine regulated by T-bet in this model. Together, we conclude that T-bet serves as a repressor of dermal sclerosis through an IL-13-dependent pathway in innate immune cells. T-bet, and its transcriptional network, represent an attractive target for the treatment of systemic sclerosis and other fibrosing disorders.

Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13. Publishing Authors By Initials

AO Aliprantis,J Wang,JW Fathman,R Lemaire,DM Dorfman,R Lafyatis,LH Glimcher,

For similar proteins: dna-binding proteins: t-box domain proteins research abstracts see: proteins: dna-binding proteins: t-box domain proteins research

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Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 2827-30

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 16

MONTH: 02

YEAR: 2007

Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13. Keywords Mesh Terms:

KEYWORDS: T-Box Domain Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13. Information

Substance Name: Bleomycin

Registry Number: 11056-06-7

Grant and Affiliation Information for Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13.

AFFILIATION: Department of Infectious Diseases and Immunology, Harvard School of Public Health, 651 Huntington Avenue, Boston, MA 02115, USA.

Country: United States

AGENCY: United States NIAID

GRANT: K08 AI 57434

ACRONYM: AI

MEDLINETA: Proc Natl Acad Sci U S A

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