Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Trichuris muris infection drives cell-intrinsic IL4R alpha independent large intestinal RELMα+ macrophages.

ABSTRACT: The RELMα+ macrophage phenotype associates with the presence of anti-inflammatory macrophages and work in other model systems has demonstrated that the balance of pro-inflammatory and anti-inflammatory macrophages is critically important in enabling the resolution of inflammation. Moreover, in the context of type 2 immunity, RELMα+ anti-inflammatory macrophages are associated with the activation of macrophages via the IL4Ra. Despite a breadth of inflammatory pathologies associated with the large intestine, including those that accompany parasitic infection, it is not known about how large intestinal macrophages are activated towards an anti-inflammatory phenotype.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Mus musculus

SUBMITTER: Leo Zeef

PROVIDER: E-MTAB-10501 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Type I interferon in patients with systemic autoimmune rheumatic disease is associated with haematological abnormalities and specific autoantibody profiles.

Reynolds John A JA Briggs Tracy A TA Rice Gillian I GI Darmalinggam Sathya S Bondet Vincent V Bruce Ellen E Khan Mumtaz M Haque Sahena S Chinoy Hector H Herrick Ariane L AL McCarthy Eoghan M EM Zeef Leo L Hayes Andrew A Duffy Darragh D Parker Ben B Bruce Ian N IN

Arthritis research & therapy 20190614 1

<h4>Objectives</h4>To investigate the relationships between interferon alpha (IFNα) and the clinical and serological phenotype of patients with systemic autoimmune rheumatic disease (SARDs) in order to determine whether a distinct subpopulation of patients can be identified.<h4>Methods</h4>We recruited patients with at least 1 SARD clinical feature and at least 1 SARD-related autoantibody from two NHS Trusts in Greater Manchester. A 6-gene interferon-stimulated gene (ISG) score was calculated in ...[more]

PMID: 31200750

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Project description:Interferon (IFN)γ and interleukin (IL)-4 are central regulators of T helper 1 (Th1) and T helper 2 (Th2) immune responses, respectively. Both cytokines have a major impact on macrophage phenotypes: IFNγ–priming and subsequent TLR4 activation induces so called classically activated macrophages that are characterized by pronounced pro-inflammatory responses, whereas IL-4–treated macrophages, commonly called alternatively activated, are known to develop enhanced capacity for endocytosis, antigen presentation, and tissue repair and are generally considered anti-inflammatory. Considering IL-4 as priming rather than activating stimulus, we now compared the TLR4–dependent global gene activation program in IFNγ– versus IL-4–pretreated mouse macrophages, which has rarely been studied so far. Although both cytokines frequently induced opposing effects on gene transcription, the subsequent activation of bone marrow-derived macrophages by lipopolysaccharide (LPS) produced a strong, priming dependent pro-inflammatory response in both macrophage types. For example, the production of key pro-inflammatory cytokines IL-6 and IL-12 was significantly higher in IL-4– versus IFNγ–primed macrophages and several cytokine genes, including Il19, Ccl17, Ccl22, Ccl24 and Cxcl5, were preferentially induced in alternatively primed and LPS activated mouse macrophages. In a subset of genes, including IL12a, IFNγ priming was actually found to suppress LPS–induced gene expression in a Stat1–dependent manner. Our data suggest that IL-4–priming is not per se anti-inflammatory but generates a macrophage that is “tissue protective” but still capable of mounting a strong inflammatory response after TLR4–dependent activation. Keywords: Gene expression profiling Gene expression was investigated in mouse bone marrow-derived macrophages (BMM). On day 7, BMM were stimulated with either IL-4 or IFNγ overnight (18h in total). LPS treatment was performed in primed and unprimed macrophages 4 h prior to harvesting. At least three independent experiments were performed for each condition.

Dataset Information

Trichuris muris infection drives cell-intrinsic IL4R alpha independent large intestinal RELMα+ macrophages.

Publications

Type I interferon in patients with systemic autoimmune rheumatic disease is associated with haematological abnormalities and specific autoantibody profiles.

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