Mucosal Immunology Section
Mucosal Immunology Section
Wilhelm C.,Mucosal Immunology Section |
Wilhelm C.,University of Bonn |
Harrison O.J.,Mucosal Immunology Section |
Schmitt V.,University of Bonn |
And 8 more authors.
Journal of Experimental Medicine | Year: 2016
Innate lymphoid cells (ILC) play an important role in many immune processes, including control of infections, inflammation, and tissue repair. To date, little is known about the metabolism of ILC and whether these cells can metabolically adapt in response to environmental signals. Here we show that type 2 innate lymphoid cells (ILC2), important mediators of barrier immunity, predominantly depend on fatty acid (FA) metabolism during helminth infection. Further, in situations where an essential nutrient, such as vitamin A, is limited, ILC2 sustain their function and selectively maintain interleukin 13 (IL-13) production via increased acquisition and utilization of FA. Together, these results reveal that ILC2 preferentially use FAs to maintain their function in the context of helminth infection or malnutrition and propose that enhanced FA usage and FA-dependent IL-13 production by ILC2 could represent a host adaptation to maintain barrier immunity under dietary restriction.
Zanvit P.,Mucosal Immunology Section |
Konkel J.E.,Mucosal Immunology Section |
Konkel J.E.,University of Manchester |
Jiao X.,Mucosal Immunology Section |
And 16 more authors.
Nature Communications | Year: 2015
Psoriasis is an inflammatory skin disease affecting a 1/42% of the worlda € s population, but the aetiology remains incompletely understood. Recently, microbiota have been shown to differentially regulate the development of autoimmune diseases, but their influence on psoriasis is incompletely understood. We show here that adult mice treated with antibiotics that target Gram-negative and Gram-positive bacteria develop ameliorated psoriasiform dermatitis induced by imiquimod, with decreased pro-inflammatory IL-17- and IL-22-producing T cells. Surprisingly, mice treated neonatally with these antibiotics develop exacerbated psoriasis induced by imiquimod or recombinant IL-23 injection when challenged as adults, with increased IL-22-producing I 3I + T cells. 16S rRNA gene compositional analysis reveals that neonatal antibiotic-treatment dysregulates gut and skin microbiota in adults, which is associated with increased susceptibility to experimental psoriasis. This link between neonatal antibiotic-mediated imbalance in microbiota and development of experimental psoriasis provides precedence for further investigation of its specific aetiology as it relates to human psoriasis. © 2015 Macmillan Publishers Limited. All rights reserved.
Hall B.E.,U.S. National Institutes of Health |
Wankhade U.D.,Mucosal Immunology Section |
Konkel J.E.,Cell Regulation and Control Unit |
Cherukuri K.,U.S. National Institutes of Health |
And 6 more authors.
Journal of Biological Chemistry | Year: 2013
Three homologues of TGF-β exist in mammals as follows: TGF-β1, TGF-β2, and TGF-β3. All three proteins share high homology in their amino acid sequence, yet each TGF-β isoform has unique heterologous motifs that are highly conserved during evolution. Although these TGF-β proteins share similar properties in vitro, isoform-specific properties have been suggested through in vivo studies and by the unique phenotypes for each TGF-β knock-out mouse. To test our hypothesis that each of these homologues has nonredundant functions, and to identify such isoform-specific roles, we genetically exchanged the coding sequence of the mature TGF-β1 ligand with a sequence from TGF-β3 using targeted recombination to create chimeric TGF- β1β knock-in mice (TGF-βLβ3β3). In the TGF-βLβ3β3 mouse, localization and activation still occur through the TGF-β1 latent associated peptide, but cell signaling is triggered through the TGF-β3 ligand that binds to TGF-β receptors. Unlike TGF-β1-/- mice, the TGF-β1Lβ3β3 mice show neither embryonic lethality nor signs of multifocal inflammation, demonstrating that knock-in of the TGF-β3 ligand can prevent the vasculogenesis defects and autoimmunity associated with TGF-β1 deficiency. However, the TGF-β1Lβ3β3 mice have a shortened life span and display tooth and bone defects, indicating that the TGF-β homologues are not completely interchangeable. Remarkably, the TGF-β1 Lβ3β3 mice display an improved metabolic phenotype with reduced body weight gain and enhanced glucose tolerance by induction of beneficial changes to the white adipose tissue compartment. These findings reveal both redundant and unique nonoverlapping functional diversity in TGF-β isoform signaling that has relevance to the design of therapeutics aimed at targeting the TGF-β pathway in human disease. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
PubMed | Mucosal Immunology Section
Type: Journal Article | Journal: European journal of immunology | Year: 2015
CD4(+) regulatory T cells expressing the transcription factor Foxp3 can be generated in the thymus (tTreg cells), but the cellular and molecular pathways driving their development remain incompletely understood. TGF- is essential for the generation of Foxp3(+) Treg cells converted from peripheral nave CD4(+) T cells (pTreg cells), yet a role for TGF- in tTreg-cell development was initially refuted. Nevertheless, recent studies have unmasked a requirement for TGF- in the generation of tTreg cells. Experimental evidence reveals that TGF-in the context of TCR stimulation induces Foxp3 gene transcription in thymic Treg precursors, CD4(+) CD8(-) CD25(-) semimature and mature single-positive thymocytes. Intriguingly, thymic apoptosis was found to be intrinsically linked to the generation of tTreg cells, as apoptosis induced expression of TGF- intrathymically. In this short review, we will highlight key data, discuss the experimental evidence and propose a modified model of tTreg-cell development involving TGF-. We will also outline the remaining unresolved questions concerning generation of thymic Foxp3(+) Treg cells and provide our personal perspectives on the mechanisms controlling tTreg-cell development.