Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2003-5-21
pubmed:abstractText
p40, the common subunit of the proinflammatory cytokines IL-12 and IL-23, is produced by resident skin cells. Whereas the in vivo effects of IL-12 are well established, little is known about the role of IL-23 in cutaneous immune responses. In this study we show that p40 transgenic (TG) mice constitutively produce IL-23 (p19/p40), but not IL-12 (p35/p40), in basal keratinocytes by cosecretion of TG p40 with endogenous p19. Repeated injections of rIL-23 in littermate (LM) mice result in an inflammatory skin disease similar to that of p40 TG mice, confirming the proinflammatory activity of IL-23. Furthermore, IL-23 secretion by p40 TG keratinocytes induces elevated numbers of Langerhans cells (LC) with a marked up-regulation of costimulatory molecules, indicating advanced maturation of keratin 14 (K14)/p40 LC when compared with LM LC. At the functional level, freshly isolated K14/p40 LC greatly exceeded LC from LM animals in their capacity to stimulate allogeneic T cell proliferation. To assess whether IL-23 regulates cutaneous immune responses in vivo, we used an allogeneic skin transplantation model. Full thickness skin grafts from K14/p40 donors (H-2(q)) transplanted across a MHC class I and class II barrier onto BALB/c (H-2(d)) recipients were rejected in a significantly accelerated fashion (mean survival time: 8.8 days) when compared with skin grafts from non-TG LM (H-2(q)) (mean survival time: 10.7 days, p < 0.01). Based on these results we propose that IL-23-induced changes of LC may be an important mechanism in directing the outcome of cutaneous immune responses.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
170
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5438-44
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12759419-Animals, pubmed-meshheading:12759419-Cell Count, pubmed-meshheading:12759419-Cell Movement, pubmed-meshheading:12759419-Cells, Cultured, pubmed-meshheading:12759419-Female, pubmed-meshheading:12759419-Graft Rejection, pubmed-meshheading:12759419-Immunity, Cellular, pubmed-meshheading:12759419-Immunophenotyping, pubmed-meshheading:12759419-Inflammation, pubmed-meshheading:12759419-Injections, Subcutaneous, pubmed-meshheading:12759419-Interleukin-12, pubmed-meshheading:12759419-Interleukin-12 Subunit p40, pubmed-meshheading:12759419-Interleukin-23, pubmed-meshheading:12759419-Interleukin-23 Subunit p19, pubmed-meshheading:12759419-Interleukins, pubmed-meshheading:12759419-Interphase, pubmed-meshheading:12759419-Keratin-14, pubmed-meshheading:12759419-Keratins, pubmed-meshheading:12759419-Langerhans Cells, pubmed-meshheading:12759419-Lymphocyte Activation, pubmed-meshheading:12759419-Lymphocyte Culture Test, Mixed, pubmed-meshheading:12759419-Mice, pubmed-meshheading:12759419-Mice, Inbred BALB C, pubmed-meshheading:12759419-Mice, Transgenic, pubmed-meshheading:12759419-Organ Culture Techniques, pubmed-meshheading:12759419-Protein Subunits, pubmed-meshheading:12759419-RNA, Messenger, pubmed-meshheading:12759419-Skin, pubmed-meshheading:12759419-Skin Diseases, pubmed-meshheading:12759419-Skin Transplantation
pubmed:year
2003
pubmed:articleTitle
IL-23 production by cosecretion of endogenous p19 and transgenic p40 in keratin 14/p40 transgenic mice: evidence for enhanced cutaneous immunity.
pubmed:affiliation
Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, University of Vienna Medical School, Vienna International Research Cooperation Center, Vienna, Austria. tamara.kopp@ahk-wien.ac.at
pubmed:publicationType
Journal Article