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Homozygous IL37 mutation associated with infantile inflammatory bowel disease

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dc.contributor.authorÖZEN, AHMET OĞUZHAN
dc.contributor.authorsZhang, Zinan Z.; Zhang, Yu; He, Tingyan; Sweeney, Colin L.; Baris, Safa; Karakoc-Aydiner, Elif; Yao, Yikun; Ertem, Deniz; Matthews, Helen F.; Gonzaga-Jauregui, Claudia; Malech, Harry L.; Su, Helen C.; Ozen, Ahmet; Smith, Kenneth G. C.; Lenardo, Michael J.
dc.date.accessioned2022-03-14T09:56:26Z
dc.date.available2022-03-14T09:56:26Z
dc.date.issued2021-03-09
dc.description.abstractInterleukin (IL)-37, an antiinflammatory IL-1 family cytokine, is a key suppressor of innate immunity. IL-37 signaling requires the heterodimeric IL-18R1 and IL-1R8 receptor, which is abundantly expressed in the gastrointestinal tract. Here we report a 4-mo-old male from a consanguineous family with a homozygous loss-of-function IL37 mutation. The patient presented with persistent diarrhea and was found to have infantile inflammatory bowel disease (I-IBD). Patient cells showed increased intracellular IL-37 expression and increased proinflammatory cytokine production. In cell lines, mutant IL-37 was not stably expressed or properly secreted and was thus unable to functionally suppress proinflammatory cytokine expression. Furthermore, induced pluripotent stem cell-derived macrophages from the patient revealed an activated macrophage phenotype, which is more prone to lipopolysaccharide and IL-1 beta stimulation, resulting in hyperinflammatory tumor necrosis factor production. Insights from this patient will not only shed light on monogenic contributions of I-IBD but may also reveal the significance of the IL-18 and IL-37 axis in colonic homeostasis.
dc.identifier.doi10.1073/pnas.2009217118
dc.identifier.issn0027-8424
dc.identifier.pubmed33674380
dc.identifier.urihttps://hdl.handle.net/11424/243720
dc.identifier.wosWOS:000627429100016
dc.language.isoeng
dc.publisherNATL ACAD SCIENCES
dc.relation.ispartofPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectimmunodeficiency
dc.subjectinflammatory bowel disease
dc.subjectIBD
dc.subjectIL37
dc.subjectVEO-IBD
dc.subjectIL-37
dc.subjectEXPRESSION
dc.subjectSIGIRR
dc.titleHomozygous IL37 mutation associated with infantile inflammatory bowel disease
dc.typearticle
dspace.entity.typePublication
local.avesis.id7bcb97c6-9040-4bfa-a181-b1913031f3e0
local.import.packageSS16
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.articlenumbere2009217118
local.journal.numberofpages3
oaire.citation.issue10
oaire.citation.titlePROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
oaire.citation.volume118
relation.isAuthorOfPublication3e9c297b-e636-4836-8f61-dc9c8b7c29cf
relation.isAuthorOfPublication.latestForDiscovery3e9c297b-e636-4836-8f61-dc9c8b7c29cf

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