Homeostatic tissue responses in skin biopsies from NOMID patients with constitutive overproduction of IL-1β.
The autoinflammatory disorder, Neonatal-onset Multisystem Inflammatory Disease (NOMID) is the most severe phenotype of disorders caused by mutations in CIAS1 that result in increased production and secretion of active IL-1β. NOMID patients present with systemic and organ-specific inflammation of the...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2012
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/8a9aeb4526b5468588188cde3238cfac |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:8a9aeb4526b5468588188cde3238cfac |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:8a9aeb4526b5468588188cde3238cfac2021-11-18T08:06:58ZHomeostatic tissue responses in skin biopsies from NOMID patients with constitutive overproduction of IL-1β.1932-620310.1371/journal.pone.0049408https://doaj.org/article/8a9aeb4526b5468588188cde3238cfac2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23226210/?tool=EBIhttps://doaj.org/toc/1932-6203The autoinflammatory disorder, Neonatal-onset Multisystem Inflammatory Disease (NOMID) is the most severe phenotype of disorders caused by mutations in CIAS1 that result in increased production and secretion of active IL-1β. NOMID patients present with systemic and organ-specific inflammation of the skin, central nervous system and bone, and respond dramatically to treatment with IL-1 blocking agents. We compared the cellular infiltrates and transcriptome of skin biopsies from patients with NOMID (n = 14) before treatment (lesional (LS) and non-lesional (pre-NL) skin) and after treatment (post-NL) with the IL-1 blocker anakinra (recombinant IL-1 receptor antagonist, Kineret®, Swedish Orphan Biovitrum AB, SOBI), to normal skin (n = 5) to assess tissue responses in the context of untreated and treated disease. Abundant neutrophils distinguish LS skin from pre-NL and post-NL skin. CD11c(+) dermal dendritic cells and CD163(+) macrophages expressed activated caspase-1 and are a likely source of cutaneous IL-1 production. Treatment with anakinra led to the disappearance of neutrophils, but CD3(+) T cells and HLA-DR(+) cells remained elevated. Among the upregulated genes IL-6, IL-8, TNF, IL-17A, CCL20, and the neutrophil defensins DEFA1 and DEFA3 were differentially regulated in LS tissues (compared to normal skin). Important significantly downregulated pathways in LS skin included IL-1R/TLR signaling, type I and II cytokine receptor signaling, mitochondrial dysfunction, and antigen presentation. The differential expression and regulation of microRNAs and pathways involved in post-transcriptional modification were suggestive of epigenetic modification in the chronically inflamed tissue. Overall, the dysregulated genes and pathways suggest extensive "adaptive" mechanisms to control inflammation and maintain tissue homeostasis, likely triggered by chronic IL-1 release in the skin of patients with NOMID.Pamela AubertMayte Suárez-FariñasHiroshi MitsuiLeanne M Johnson-HuangJamie Lynn HardenKatherine C PiersonJoseph G DolanInna NovitskayaIsrael CoatsJacob EstesEdward W CowenNicole PlassChyi-Chia Richard LeeHong-Wei SunMichelle A LowesRaphaela Goldbach-ManskyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e49408 (2012) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Pamela Aubert Mayte Suárez-Fariñas Hiroshi Mitsui Leanne M Johnson-Huang Jamie Lynn Harden Katherine C Pierson Joseph G Dolan Inna Novitskaya Israel Coats Jacob Estes Edward W Cowen Nicole Plass Chyi-Chia Richard Lee Hong-Wei Sun Michelle A Lowes Raphaela Goldbach-Mansky Homeostatic tissue responses in skin biopsies from NOMID patients with constitutive overproduction of IL-1β. |
| description |
The autoinflammatory disorder, Neonatal-onset Multisystem Inflammatory Disease (NOMID) is the most severe phenotype of disorders caused by mutations in CIAS1 that result in increased production and secretion of active IL-1β. NOMID patients present with systemic and organ-specific inflammation of the skin, central nervous system and bone, and respond dramatically to treatment with IL-1 blocking agents. We compared the cellular infiltrates and transcriptome of skin biopsies from patients with NOMID (n = 14) before treatment (lesional (LS) and non-lesional (pre-NL) skin) and after treatment (post-NL) with the IL-1 blocker anakinra (recombinant IL-1 receptor antagonist, Kineret®, Swedish Orphan Biovitrum AB, SOBI), to normal skin (n = 5) to assess tissue responses in the context of untreated and treated disease. Abundant neutrophils distinguish LS skin from pre-NL and post-NL skin. CD11c(+) dermal dendritic cells and CD163(+) macrophages expressed activated caspase-1 and are a likely source of cutaneous IL-1 production. Treatment with anakinra led to the disappearance of neutrophils, but CD3(+) T cells and HLA-DR(+) cells remained elevated. Among the upregulated genes IL-6, IL-8, TNF, IL-17A, CCL20, and the neutrophil defensins DEFA1 and DEFA3 were differentially regulated in LS tissues (compared to normal skin). Important significantly downregulated pathways in LS skin included IL-1R/TLR signaling, type I and II cytokine receptor signaling, mitochondrial dysfunction, and antigen presentation. The differential expression and regulation of microRNAs and pathways involved in post-transcriptional modification were suggestive of epigenetic modification in the chronically inflamed tissue. Overall, the dysregulated genes and pathways suggest extensive "adaptive" mechanisms to control inflammation and maintain tissue homeostasis, likely triggered by chronic IL-1 release in the skin of patients with NOMID. |
| format |
article |
| author |
Pamela Aubert Mayte Suárez-Fariñas Hiroshi Mitsui Leanne M Johnson-Huang Jamie Lynn Harden Katherine C Pierson Joseph G Dolan Inna Novitskaya Israel Coats Jacob Estes Edward W Cowen Nicole Plass Chyi-Chia Richard Lee Hong-Wei Sun Michelle A Lowes Raphaela Goldbach-Mansky |
| author_facet |
Pamela Aubert Mayte Suárez-Fariñas Hiroshi Mitsui Leanne M Johnson-Huang Jamie Lynn Harden Katherine C Pierson Joseph G Dolan Inna Novitskaya Israel Coats Jacob Estes Edward W Cowen Nicole Plass Chyi-Chia Richard Lee Hong-Wei Sun Michelle A Lowes Raphaela Goldbach-Mansky |
| author_sort |
Pamela Aubert |
| title |
Homeostatic tissue responses in skin biopsies from NOMID patients with constitutive overproduction of IL-1β. |
| title_short |
Homeostatic tissue responses in skin biopsies from NOMID patients with constitutive overproduction of IL-1β. |
| title_full |
Homeostatic tissue responses in skin biopsies from NOMID patients with constitutive overproduction of IL-1β. |
| title_fullStr |
Homeostatic tissue responses in skin biopsies from NOMID patients with constitutive overproduction of IL-1β. |
| title_full_unstemmed |
Homeostatic tissue responses in skin biopsies from NOMID patients with constitutive overproduction of IL-1β. |
| title_sort |
homeostatic tissue responses in skin biopsies from nomid patients with constitutive overproduction of il-1β. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/8a9aeb4526b5468588188cde3238cfac |
| work_keys_str_mv |
AT pamelaaubert homeostatictissueresponsesinskinbiopsiesfromnomidpatientswithconstitutiveoverproductionofil1b AT maytesuarezfarinas homeostatictissueresponsesinskinbiopsiesfromnomidpatientswithconstitutiveoverproductionofil1b AT hiroshimitsui homeostatictissueresponsesinskinbiopsiesfromnomidpatientswithconstitutiveoverproductionofil1b AT leannemjohnsonhuang homeostatictissueresponsesinskinbiopsiesfromnomidpatientswithconstitutiveoverproductionofil1b AT jamielynnharden homeostatictissueresponsesinskinbiopsiesfromnomidpatientswithconstitutiveoverproductionofil1b AT katherinecpierson homeostatictissueresponsesinskinbiopsiesfromnomidpatientswithconstitutiveoverproductionofil1b AT josephgdolan homeostatictissueresponsesinskinbiopsiesfromnomidpatientswithconstitutiveoverproductionofil1b AT innanovitskaya homeostatictissueresponsesinskinbiopsiesfromnomidpatientswithconstitutiveoverproductionofil1b AT israelcoats homeostatictissueresponsesinskinbiopsiesfromnomidpatientswithconstitutiveoverproductionofil1b AT jacobestes homeostatictissueresponsesinskinbiopsiesfromnomidpatientswithconstitutiveoverproductionofil1b AT edwardwcowen homeostatictissueresponsesinskinbiopsiesfromnomidpatientswithconstitutiveoverproductionofil1b AT nicoleplass homeostatictissueresponsesinskinbiopsiesfromnomidpatientswithconstitutiveoverproductionofil1b AT chyichiarichardlee homeostatictissueresponsesinskinbiopsiesfromnomidpatientswithconstitutiveoverproductionofil1b AT hongweisun homeostatictissueresponsesinskinbiopsiesfromnomidpatientswithconstitutiveoverproductionofil1b AT michellealowes homeostatictissueresponsesinskinbiopsiesfromnomidpatientswithconstitutiveoverproductionofil1b AT raphaelagoldbachmansky homeostatictissueresponsesinskinbiopsiesfromnomidpatientswithconstitutiveoverproductionofil1b |
| _version_ |
1718422180742561792 |