The activating protein 1 transcription factor basic leucine zipper transcription factor, ATF-like (BATF), regulates lymphocyte- and mast cell–driven immune responses in the setting of allergic asthma

Übel, Caroline; Sopel, Nina; Graser, Anna; Hildner, Kai; Reinhardt, Cornelia; Zimmermann, Theodor; Rieker, Ralf J.; Maier, Anja; Neurath, Markus F.; Murphy, Kenneth M.; Finotto, Susetta

doi:10.1016/j.jaci.2013.09.049

Cited by 50 publications

(50 citation statements)

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“…BATF is critical for Th17 differentiation and IL-17 production though interactions with IRF4 [210–214]. Additionally, recent studies suggest that BATF may play a larger role in Th2 cytokine production than previously appreciated [215–217]. Thus, more thorough investigation of cooperating interactions between c-Maf and BATF in Th2 and Tfh cytokine production may reveal novel pathways involved in non-classical IL-4 production (figure 1).…”

Section: Potential Pathways For Non-classical Il-4 Production In Tfh mentioning

confidence: 99%

The differential expression of IL-4 and IL-13 and its impact on type-2 immunity

2015

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Allergic disease represents a significant global health burden, and disease incidence continues to rise in urban areas of the world. As such, a better understanding of the basic immune mechanisms underlying disease pathology are likely the key to developing therapeutic interventions to both prevent disease onset as well as to ameliorate disease morbidity in those individuals already suffering from a disorder linked to type-2 inflammation. Two factors central to type-2 immunity are interleukin(IL)-4 and IL-13. These two cytokines have been linked to virtually all of the major disease hallmarks associated with type-2 inflammation. Therefore, IL-4 and IL-13 and their regulatory pathways represent ideal targets to suppress disease. However, despite sharing many common regulatory pathways and receptors, these cytokines perform very distinct functions during a type-2 immune response. This review summarizes the literature surrounding the function and expression of IL-4 and IL-13 in CD4+ T cells and innate immune cells. It highlights recent in vivo findings regarding the differential expression and non-canonical regulation of IL-4 and IL-13 in various immune cells, which likely play an underappreciated and important role in type-2 allergic immunity.

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Section: Potential Pathways For Non-classical Il-4 Production In Tfh mentioning

confidence: 99%

The differential expression of IL-4 and IL-13 and its impact on type-2 immunity

2015

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“…Models of ovalbumin (OVA)-induced allergic airway inflammation show reduced type-2 cytokine expression and allergic hallmarks in Batf −/− lungs (15, 20, 22) regardless of the genetic background (BALB/c and C57BL/6) or different targeting strategies used for the generation of Batf −/− mice (14, 18). However, despite a clear decrease in allergic inflammation, a consensus as to the mechanisms involved has not been reached.…”

Section: Introductionmentioning

confidence: 99%

“…Currently, increased Th1 cell accumulation and defects in Th9 development, Th17 cell generation, and Tfh cell function have all been used to explain the diminished type-2 inflammation found in Batf −/− mice (15, 20, 22). Although defects in Th2 cell function and generation have been implied as a result of data obtained from bulk cultures or total tissue extracts from Batf −/− lungs (20, 22), a recent study concluded that Th2 differentiation and IL-4 production remain largely intact after ovalbumin sensitization and challenge of Batf −/− mice (15). As such, further studies are needed to understand the full impact of BATF-mediated regulation in type-2 immunity and Th2 cell biology.…”

Section: Introductionmentioning

confidence: 99%

BATF Modulates the Th2 Locus Control Region and Regulates CD4+ T Cell Fate during Antihelminth Immunity

Bao

Carr

et al. 2016

The Journal of Immunology

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The AP-1 factor, basic leucine zipper transcription factor, ATF-like (BATF) is important for CD4+ T-helper (Th) 17, Th9 and follicular T helper (Tfh) cell development. However, its precise role in Th2 differentiation and function remains unclear, and the necessity of BATF in non-allergic settings of type-2 immunity has not been explored. Here, we show that in response to parasitic helminths, Batf−/− mice are unable to generate both Tfh and Th2 cells. As a consequence, Batf−/− mice fail to establish productive type-2 immunity during primary and secondary infection. Batf−/− CD4+ T cells do not achieve type-2 cytokine competency, which implies that BATF plays a key role in the regulation of interleukin(IL)-4 and IL-13. In contrast to Th17 and Th9 cell subsets where BATF binds directly to promoter and enhancer regions to regulate cytokine expression, our results show that BATF is significantly enriched at Rad50 hypersensitivity sites (RHS) 6 and 7 of the locus control region (LCR) relative to AP-1 sites surrounding type-2 cytokine loci in Th2 cells. Indeed, Batf−/− CD4+ T cells do not obtain permissive epigenetic modifications within the Th2 locus, which have been linked to RHS6 and RHS7 function. In sum, these findings reveal BATF as a central modulator of peripheral and humoral hallmarks of type-2 immunity, and begin to elucidate a novel mechanism by which BATF regulates type-2 cytokine production through its modification of the Th2 LCR.

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“…Thus, miR-21 and miR-16 may play a role in the UVB-induced immunosuppressive response via down-regulating immune-related genes. In addition, GPR183 , PTPRC and PLEK are all targeted by TFs BATF , SPI1 and EP300 , which have been demonstrated to be involved in the immune system [46–48]. Notably, we also observed interactions of EP300 with other down-regulated DEGs in the screened module.…”

Section: Discussionmentioning

confidence: 51%

Potential molecular characteristics in situ in response to repetitive UVB irradiation

Chen

Zhang

2016

Diagn Pathol

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BackgroundTo identify molecular characteristics in situ in response to repetitive UVB (ultraviolet-B) irradiation.MethodsMicroarray data from the Gene Expression Omnibus were re-analyzed to identify DEGs (differentially expressed genes) between UVB-irradiated and non-irradiated skin biopsies. Enrichment and annotation analyses were performed respectively using DAVID, and TSGene and TAG databases. PPIs (protein-protein interactions) were analyzed using STRING, and miRNAs (microRNAs) and TFs (transcription factors) were predicted separately by miRNA-related databases and ENCODE. Accordingly, the PPI network and regulatory networks were visualized using Cytoscape, and they were merged together to obtain an integrated network for mining densely connected modules.ResultsAltogether, 151 up- and 64 down-regulated genes were identified between UVB-irradiated and non-irradiated skin biopsies, among which down-regulated DNAJB4 and SLIT2 were annotated as tumor-suppressors and up-regulated KIT was annotated as an oncogene. The up-regulated DEGs were significantly enriched in biological processes related to pigmentation (DCT, SOX10, TYRP1, TYR, MLPH, KIT and GPR143), while the down-regulated DEGs were dramatically related to haemopoiesis and the immune system (GPR183, INHBA, PTPRC, PLEK, CD8A and IKZF1). Furthermore, many miRNAs were screened for the DEGs, including miR-206 and miR-496 targeting KIT, miR-184 targeting DCT, and highly significant miR-337-5p, miR-21 and miR-16. Additionally, TFs were identified for the DEGs, among which PAX5 and HNF4A targeted MLPH and GPR143, respectively, while BATF, SPI1 and EP300 jointly target GPR183, PTPRC and PLEK.ConclusionsThe pigmentation and immune system implicated by DEGs, miRNAs and TFs might be important molecular mechanisms in response to UVB irradiation.

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The activating protein 1 transcription factor basic leucine zipper transcription factor, ATF-like (BATF), regulates lymphocyte- and mast cell–driven immune responses in the setting of allergic asthma

Cited by 50 publications

References 37 publications

The differential expression of IL-4 and IL-13 and its impact on type-2 immunity

The differential expression of IL-4 and IL-13 and its impact on type-2 immunity

BATF Modulates the Th2 Locus Control Region and Regulates CD4+ T Cell Fate during Antihelminth Immunity

Potential molecular characteristics in situ in response to repetitive UVB irradiation

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