ArticleAmerican journal of respiratory cell and molecular biology2012
Protective role of T-bet and Th1 cytokines in pulmonary graft-versus-host disease and peribronchiolar fibrosis.
Article in American journal of respiratory cell and molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Unique Immune Polarization of the Lung Allograft: Implications for Organ-specific Immunoregulation and Tolerance Induction.Transplantation · 2026Review
- Zwitterionic hydrogel designs for conducting polymers enable bioelectronics with suppressed foreign body responses.bioRxiv : the preprint server for biology · 2025Article
- A Nasal Inflammatory Cytokine Signature Is Associated with Early Graft-versus-Host Disease of the Lung after Allogeneic Hematopoietic Cell Transplantation: Proof of Concept.ImmunoHorizons · 2023Observational
- Dissecting the regulatory network of transcription factors in T cell phenotype/functioning during GVHD and GVT.Frontiers in immunology · 2023Review
- IL-17A Contributes to Lung Fibrosis in a Model of Chronic Pulmonary Graft-versus-host Disease.Transplantation · 2019Article
- SYK inhibitor entospletinib prevents ocular and skin GVHD in mice.JCI insight · 2018Article
- Genetic Adjuvantation of a Cell-Based Therapeutic Vaccine for Amelioration of Chagasic Cardiomyopathy.Infection and immunity · 2017Article
- Cytokine mediators of chronic graft-versus-host disease.The Journal of clinical investigation · 2017Review
- Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop.JCI insight · 2017Review
- The Inflammatory Cytokine IL-21 is Expressed by Splenic Neutrophils in Response to Transplantation of Allogeneic Cells.SOJ immunology · 2016Article
- CD8(+)IL-17(+) T Cells Mediate Neutrophilic Airway Obliteration in T-bet-Deficient Mouse Lung Allograft Recipients.American journal of respiratory cell and molecular biology · 2015Article
- Various forms of tissue damage and danger signals following hematopoietic stem-cell transplantation.Frontiers in immunology · 2015Review
- Impaired CD8(+) T cell immunity after allogeneic bone marrow transplantation leads to persistent and severe respiratory viral infection.Transplant immunology · 2015Article
- T-bet is critical for the development of acute graft-versus-host disease through controlling T cell differentiation and function.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- The complex and central role of interferon-γ in graft-versus-host disease and graft-versus-tumor activity.Immunological reviews · 2014Review
- The Th17 pathway and inflammatory diseases of the intestines, lungs, and skin.Annual review of pathology · 2013Review
- Current data on IL-17 and Th17 cells and implications for graft versus host disease.Einstein (Sao Paulo, Brazil)Review
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7 authors at 3 institutions in 1 country.
Funding
Abstract
T-box expressed in T cells (T-bet) is a critical transcription factor for T helper (Th) 1 responses. Although Th1 cells are thought to contribute to certain alloimmune responses, their role in pulmonary graft-versus-host disease (GVHD) is uncertain. We have established a murine model of acute pulmonary GVHD after hematopoietic cell transplant (HCT) and inhaled LPS exposure. We tested the hypothesis that pulmonary GVHD can occur independent of Th1 cells using T-bet-deficient donors. B10.BR(H2(k)) mice underwent allogeneic (Allo) or syngeneic (Syn) HCT with cells from either C57Bl/6J(H2(b)) mice (Allo wild-type [WT] or SynWT) or C57Bl/6J mice lacking T-bet (AlloTbet(-/-) or SynTbet(-/-)). After HCT, mice were exposed daily to aerosolized LPS and subsequently bronchoalveolar lavage and lung tissue were analyzed for cytokines, lymphocytic inflammation, pathology, and fibrosis. Independent of LPS exposure, AlloTbet(-/-) mice developed pulmonary GVHD manifested by lymphocytic inflammation. Furthermore, AlloTbet(-/-) mice developed features of chronic pulmonary GVHD, including increased peribronchiolar fibrosis and collagen content. LPS exposure increased neutrophil recruitment and decreased static compliance in AlloTbet(-/-) mice as compared with LPS-exposed AlloWT mice or LPS-exposed SynTbet(-/-) mice. In addition, LPS-exposed AlloTbet(-/-) mice had increased pulmonary IL-17, IL-13, and Th17 cells, and diminished regulatory T cells compared with the other groups. Our results demonstrate that Th1 cytokines are dispensable in pulmonary GVHD. In the absence of T-bet, there is increased production of Th17 and Th2 cytokines that is associated with peribronchiolar fibrosis and is further enhanced by LPS. These results suggest that the interplay between local innate immunity and non-Th1 T cell subsets contribute to chronic pulmonary GVHD.
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