Transcription factor IRF4 drives dendritic cells to promote Th2 differentiation

Williams, Jesse W.; Tjota, Melissa Y.; Clay, Bryan S.; Lugt, Bryan Vander; Bandukwala, Hozefa S.; Hrusch, Cara L.; Decker, Donna C.; Blaine, Kelly M.; Fixsen, Bethany; Singh, Harinder; Sciammas, Roger; Sperling, Anne I.

doi:10.1038/ncomms3990

Cited by 337 publications

(336 citation statements)

References 65 publications

Supporting

Mentioning

300

Contrasting

Unclassified

Order By: Relevance

“…The transcription factor IRF4, which is required for the maturation, migration, and function of skin DC in LN (25,49,50), was also expressed, but its levels were similar in all DC regardless of Nb loading or treatment. This latter finding aligns with recent reports showing that IRF4 is necessary for the generation of Th2 responses (25,51), but also suggests that IRF4 is unlikely to represent a polarizing signal that determines the ability of DC from Nb-treated mice to prime for IL-4 production. Thus, our data suggest that PDL2…”

Section: Discussionsupporting

confidence: 78%

Helminth-Conditioned Dendritic Cells Prime CD4+ T Cells to IL-4 Production In Vivo

Connor

Tang

Camberis

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

Dendritic cells (DC) are critical for the initiation of immune responses; however, their role in priming IL-4–producing Th2 cells in vivo is not fully understood. We used a model of intradermal injection with fluorescent-labeled, nonviable larvae from the helminth parasite nonviable Nippostrongylus brasiliensis L3 larvae (Nb), a strong inducer of Th2 responses, together with IL-4–GFP reporter mice that enable a sensitive detection of IL-4 production to examine the contribution of DC to the priming of IL-4–producing CD4+ T cells in vivo. We found that parasite material is taken up by two distinct DC populations in draining lymph nodes: a mostly CD11cintMHC class II (MHCII)hiCD11b+Ly6C− dermal DC population and a CD11chiMHCIIintCD11b+Ly6C+ monocyte-derived DC population. After Nb treatment, these two DC populations appeared in the draining lymph nodes in comparable numbers and with similar kinetics; however, treatment with pertussis toxin blocked the migration of dermal DC and the priming of IL-4–producing T cells, but only partially affected monocyte-derived DC numbers. In line with this observation, transfer of OVA-loaded CD11cintMHCIIhi DC from Nb-treated mice into naive hosts could sensitize OVA-specific CD4+ T cells to IL-4 production, whereas transfer of CD11cintMHCIIhi DC from naive mice, or CD11chiMHCIIint DC from Nb-treated or naive mice, induced CD4+ T cell expansion but no IL-4 production. Phenotypic analysis of Nb-loaded CD11cintMHCIIhi DC revealed expression of programmed death ligand 2, CD301b, IFN regulatory factor 4, and moderate upregulation of OX40 ligand. However, thymic stromal lymphopoietin and OX40 ligand were not required for Th2 priming. Thus, our data suggest that appropriate stimuli can induce DC to express the unique signals sufficient to direct CD4+ T cells to Th2 differentiation.

show abstract

Section: Discussionsupporting

confidence: 78%

Helminth-Conditioned Dendritic Cells Prime CD4+ T Cells to IL-4 Production In Vivo

Connor

Tang

Camberis

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…In addition, CCR7 + CD1c + MDCs in BAL unlike the CCR7 2 counterparts expressed lower levels of CCR2 and higher levels of IRF4. CCR2, in addition to being a peripheral tissue homing receptor (47, 48), has been shown to be important in DC-elicited Th1 responses (59), whereas IRF4 has been implicated in both Th2 (49,(60)(61)(62) and Th17 responses (26,63). Taken together, this underlines the phenotypic and likely functional heterogeneity of DCs in the lungs, even within one population of CD1c + MDCs.…”

Section: Discussionmentioning

confidence: 61%

Dendritic Cells and Monocytes with Distinct Inflammatory Responses Reside in Lung Mucosa of Healthy Humans

Baharom

Schlüter

Rankin

et al. 2016

The Journal of Immunology

109

View full text Add to dashboard Cite

Every breath we take contains potentially harmful pathogens or allergens. Dendritic cells (DCs), monocytes, and macrophages are essential in maintaining a delicate balance of initiating immunity without causing collateral damage to the lungs because of an exaggerated inflammatory response. To document the diversity of lung mononuclear phagocytes at steady-state, we performed bronchoscopies on 20 healthy subjects, sampling the proximal and distal airways (bronchial wash and bronchoalveolar lavage, respectively), as well as mucosal tissue (endobronchial biopsies). In addition to a substantial population of alveolar macrophages, we identified subpopulations of monocytes, myeloid DCs (MDCs), and plasmacytoid DCs in the lung mucosa. Intermediate monocytes and MDCs were highly frequent in the airways compared with peripheral blood. Strikingly, the density of mononuclear phagocytes increased upon descending the airways. Monocytes from blood and airways produced 10-fold more proinflammatory cytokines than MDCs upon ex vivo stimulation. However, airway monocytes were less inflammatory than blood monocytes, suggesting a more tolerant nature. The findings of this study establish how to identify human lung mononuclear phagocytes and how they function in normal conditions, so that dysregulations in patients with respiratory diseases can be detected to elucidate their contribution to immunity or pathogenesis.

show abstract

“…DCs are important for T-cell activation and differentiation and subsequent IgG CSR (44,45). FLKO mice have a significantly reduced number of DCs, and previous studies on the role for FL in mediating DC-and T-cell-dependent production of IgG have rendered contradictory results (16,46).…”

Section: Discussionmentioning

confidence: 99%

Murine germinal center B cells require functional Fms-like tyrosine kinase 3 signaling for IgG1 class-switch recombination

Svensson

Andersson

Wasén

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Switched antibody classes are important for efficient immune responses. Aberrant antibody production to otherwise harmless antigens may result in autoimmunity. The protein kinase fms-like tyrosine kinase 3 receptor (Flt3) has an important role during early B-cell development, but the role of Flt3 in peripheral B cells has not been assessed before. Herein we describe a previously unappreciated role for Flt3 in IgG1 class-switch recombination (CSR) and production. We show that

show abstract

Transcription factor IRF4 drives dendritic cells to promote Th2 differentiation

Cited by 337 publications

References 65 publications

Helminth-Conditioned Dendritic Cells Prime CD4+ T Cells to IL-4 Production In Vivo

Helminth-Conditioned Dendritic Cells Prime CD4+ T Cells to IL-4 Production In Vivo

Dendritic Cells and Monocytes with Distinct Inflammatory Responses Reside in Lung Mucosa of Healthy Humans

Murine germinal center B cells require functional Fms-like tyrosine kinase 3 signaling for IgG1 class-switch recombination

Contact Info

Product

Resources

About