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IRHOM2 deficiency causes environmentally directed immunodysregulatory disease

ABSTRACT: iRHOM2 deficiency causes environmentally directed immunodysregulatory disease

PROVIDER: PRJNA741290 | ENA |

REPOSITORIES: ENA

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iRHOM2 deficiency causes environmentally directed immunodysregulatory disease

Project description:iRHOM2 deficiency causes environmentally directed immunodysregulatory disease

| PRJNA741289 | ENA

Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease

Project description:Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease

| PRJNA766689 | ENA

Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease [whole blood]

Project description:Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease [whole blood]

| PRJNA766692 | ENA

Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease [T cells]

Project description:Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease [T cells]

| PRJNA766691 | ENA

Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease [whole blood]

Project description:We report a pleiotropic disease due to loss-of-function mutations in RHBDF2, the gene encoding iRHOM2, in 2 kindreds with recurrent infections in different organs. One patient had recurrent pneumonia but no colon involvement, another had recurrent infectious hemorrhagic colitis but no lung involvement, and the other two experienced recurrent respiratory infections. Loss of iRHOM2, a rhomboid superfamily member that regulates the ADAM17 metalloproteinase, caused defective ADAM17-dependent cleavage and release of cytokines, including TNF and amphiregulin. To understand the diverse clinical phenotypes, we challenged Rhbdf2-/- mice with Pseudomonas aeruginosa by nasal gavage and observed more severe pneumonia whereas infection with Citrobacter rodentium caused worse inflammatory colitis than wild-type mice. The fecal microbiota in the colitis patient had characteristic oral species that can predispose to colitis. Thus, a new human immunodeficiency arising from iRHOM2 deficiency causes divergent disease phenotypes that can involve the local microbial environment.

2021-11-03 | GSE184876 | GEO

Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease [T cells]

2021-11-03 | GSE184875 | GEO

Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-11-03 | GSE184877 | GEO

Autosomal recessive SBNO2 deficiency causes an immunodysregulatory syndrome

Project description:Autosomal recessive SBNO2 deficiency causes an immunodysregulatory syndrome

| PRJNA781339 | ENA

Role of iRhom2 in Olfaction: Implications for Odorant Receptor Regulation and Activity-dependent Adaptation

Project description:The cell surface metalloprotease ADAM17 and its binding partners iRhom2 and iRhom1 modulate cell-cell interactions by mediating the release of membrane proteins such as TNFa and EGFR-ligands from the cell surface. Most cell types express both iRhoms, though myeloid cells exclusively express iRhom2, and iRhom1 is the main iRhom in the mouse brain. Here we report that iRhom2 is uniquely expressed in olfactory sensory neurons (OSNs), highly specialized cells expressing one olfactory receptor (OR) from a repertoire of over a thousand OR genes in mice. iRhom2-/- mice had no evident morphological defects in the olfactory epithelium (OE), yet RNAseq analysis revealed differential expression of a small subset of ORs. Notably, while the majority of ORs remain unaffected in iRhom2-/- OE, OSNs expressing ORs that are enriched in iRhom2-/- OE showed fewer gene expression changes upon odor environmental changes than the majority of OSNs. Moreover, we discovered an inverse correlation between the expression of iRhom2 compared to OSN activity genes and that odor exposure negatively regulates iRhom2 expression. Given that ORs are specialized G-protein coupled receptors (GPCRs) and many GPCRs activate iRhom2/ADAM17, we investigated if ORs could activate iRhom2/ADAM17. Activation of OR2AT4 by its agonist sandalore in keratinocytes, where this receptor is ectopically expressed, leads to ERK1/2 phosphorylation, likely via an iRhom2/ADAM17-dependent pathway. Taken together, these findings point to a mechanism by which odor stimulation of OSNs activates iRhom2/ADAM17 catalytic activity, resulting in downstream transcriptional changes to the OR repertoire and activity genes, and driving a negative feedback loop to downregulate iRhom2 expression.

2024-05-28 | GSE268171 | GEO

Genetic STAT5B immunodysregulatory disorder

Project description:Genetic STAT5B immunodysregulatory disorder

| PRJNA416162 | ENA