0000000000548615
AUTHOR
Hartmann Raifer
showing 5 related works from this author
The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8 + T cells
2013
Robust cytotoxic CD8 + T-cell response is important for immunity to intracellular pathogens. Here, we show that the transcription factor IFN Regulatory Factor 4 (IRF4) is crucial for the protective CD8 + T-cell response to the intracellular bacterium Listeria monocytogenes . IRF4-deficient ( Irf4 −/− ) mice could not clear L. monocytogenes infection and generated decreased numbers of L. monocytogenes -specific CD8 + T cells with impaired effector phenotype and function. Transfer of wild-type CD8 + T cells into Irf4 −/− mice improved bacterial clearance, suggesting an intrinsic defect of CD8 + T cells in Irf4 −/− mice. Following transfer into wild-type recipients, Irf4 −/− CD8 + T cells bec…
Microenvironmental Th9 and Th17 lymphocytes induce metastatic spreading in lung cancer.
2020
Immune microenvironment plays a critical role in lung cancer control versus progression and metastasis. In this investigation, we explored the effect of tumor-infiltrating lymphocyte subpopulations on lung cancer biology by studying in vitro cocultures, in vivo mouse models, and human lung cancer tissue. Lymphocyte conditioned media (CM) induced epithelial-mesenchymal transition (EMT) and migration in both primary human lung cancer cells and cell lines. Correspondingly, major accumulation of Th9 and Th17 cells was detected in human lung cancer tissue and correlated with poor survival. Coculturing lung cancer cells with Th9/Th17 cells or exposing them to the respective CM induced EMT in canc…
IL-17 and TNF-α Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway Inflammation
2017
Alterations of the airway microbiome is often associated with pulmonary diseases. For example, detection of the bacterial pathogen Moraxella catarrhalis in the upper airways is linked with an increased risk to develop or exacerbate asthma. However, the mechanisms by which M. cattarhalis augments allergic airway inflammation (AAI) remains unclear. We here characterized the cellular and soluble mediators of M. catarrhalis triggered excacerbation of AAI in wt and IL-17 deficient as well as in animals treated with TNF-alpha and IL-6 neutralizing antibodies. We compared the type of inflammatory response in M. catarrhalis infected, HDM-allergic and animals infected with M. catarrhalis at differen…
Reciprocal regulation of the Il9 locus by counteracting activities of transcription factors IRF1 and IRF4.
2017
The T helper 9 (Th9) cell transcriptional network is formed by an equilibrium of signals induced by cytokines and antigen presentation. Here we show that, within this network, two interferon regulatory factors (IRF), IRF1 and IRF4, display opposing effects on Th9 differentiation. IRF4 dose-dependently promotes, whereas IRF1 inhibits, IL-9 production. Likewise, IRF1 inhibits IL-9 production by human Th9 cells. IRF1 counteracts IRF4-driven Il9 promoter activity, and IRF1 and IRF4 have opposing function on activating histone modifications, thus modulating RNA polymerase II recruitment. IRF1 occupancy correlates with decreased IRF4 abundance, suggesting an IRF1-IRF4-binding competition at the I…
Tc9 cells, a new subset of CD8+T cells, support Th2-mediated airway inflammation
2013
Similar to T-helper (Th) cells, CD8(+) T cells also differentiate into distinct subpopulations. However, the existence of IL-9-producing CD8(+) T (Tc9) cells has not been elucidated so far. We show that murine CD8(+) T cells activated in the presence of IL-4 plus TGF-β develop into transient IL-9 producers characterized by specific IFN-γ and IL-10 expression patterns as well as by low cytotoxic function along with diminished expression of the CTL-associated transcription factors T-bet and Eomesodermin. Similarly to the CD4(+) counterpart, Tc9 cells required for their differentiation STAT6 and IRF4. Tc9 cells deficient for these master regulators displayed increased levels of Foxp3 that in t…