FCεRI mediates production of proinflammatory cytokines by human monocytes and monocyte-derived dendritic cells

ESDR I JSID I SID Abstracts

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CUTANEOUS LYMPHOCYTE ASSOCIATED ANTIGEN EXPRESSION IN CUTANEOUS AND MUCOUS LICHEN PLANUS &Gim6nez-Arau 0). Cristina Carrato (11.Carlos -IV, Lms Santamarm 01, Sereio Serrano 0,&G. C!amarasa,l, Departments of Dermatology (II and Pathology (4. Hospital del Mar. Ihi??tat Autbnmna de Barcelona Spain

ORGANISATION, REGULATORY SEQUENCES AND TRANSCRIPTIONAL REGULATION OF THE GENES ENCODING THE HUMAN EOSINOPHIL CHEMOATTRACTANTS EOTAXIN AND MCPI. HeinH. SchlUter C. Ktdke R CbristonIws E. Schr0der Department

Lxhen planus is characterized by a band-like dermal intlammatory infiltrate and structural alterations of the basement membrane Cell-mediated immunologuxl mechanisms and also autoimmune reaction by cytotoxx T lymphocytes have been involved in the pathogen&s. The cutaneous lymphocyte associated antigen (CLA) defined by the MoAb HECA-452 is a ceU-surface glycoprotein expressed on 41% of CDS+ T cells in normal human shn. In extracutaneous sites only about 5% of lymphocytes within T cell areas of these tissues express this ant&n whereas in inflamatorv skin lesions 85% are HECA-452 positive. We stud& CLA expresshm on T cellular cohstituents of the skin immune system of cutaneow and mucous iichen planus Thirty bmpsies previously diagnosed as lichen planus were included. eighteen from skin and twelve from mucous membranes By applying immunohistcchemical double staining, 45.71+13 85% of CD3 pahive T cells in cutaneous lichen planus were found to express HECA-452 and 23.12t14 87% m mucous lichen planus. Significant diflerences were observed @ ~0.002). in the percentage of CD-HECA452 positive cells in the inflammatory infiltrate of cutaneous and MUCOUShchen planus. Normal rabblt serum and rat IgM were used as negatwe controls. Healthy skin was also studied These results provide evidenceof different CLA expression in cutaneous and mucous membranes in lichen planus The presence of a skin homing subset of CLA-CD3 positive T lymphocytes among lichen planus mflammatory cells was confirmed Spare activation of CIA natural endothelial ligand. E-selectin. in lichen planus has been described and could explain the less percentage of Cm-CD3 positwe T cells m hchen planus with regard to other inflammatory diseases

ofDematology,

University

ofKiel,

J-M. Bat&

J

D-24105 Kid

Infiltration ofeosinophils into demul tissue is characteristic for eosinophitic in&anmatory diis like atopic dertnatitii, allergy and parasitic infections. Baaed on our recent observations of gene transcription for the eosinophil-chemotactic CC chemokina eotaxin and MCP4 in cultured dermal fibroblasts we became interested in the regulatory mechanisms governing their expression in skin. For this purpose we cloned genomic DNA tiagmznts encoding eotaxin and MCP4 to identify regulatory seqwnces. Both genes showal the 3 exon 2 intrcm structure typical for CC chemokiis and highly conserved exon&ron splice junctions. Within 150 bp ofthe 5’ untranslated region adjacent to the initiation site oftranscription we found NF-a-like

ctmsensussequen-

ces in both genes. NF-t&l elements are known to be ixdiible

but not sufficient

for TNFa induced chmnakine gene expression. Maximat transcriptional activation has been shown to require nuclear factors NF-IL6 (found in MCP4) and/or SP-1 (found in eotaxin).

Using semi-quantitative

expression

RT-PCR

we were able to show constitutive

for eotaxin and MCP4 in dermal fibroblasts

which is upregulated

mRNA by TNFa

and IFNy. The functional relevance and cell specific function of the identified transcription factor binding sites, which arc potential targets for pbammcological interventions in skin-diseases, is currently studied.

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F&RI MEDIATES PRODUCTION OF PROINFLAMMATORY CYTOKINES BY HUMAN MONOCYTES AND MONOCYTE-DERIVED DENDRITIC CELLS. No& Katoh. Thomas Bieber, Department of Dermatology, University of Bonn, Bonn, Germany The high affinity receptor for Ig!? (FceRI) is expressed on monocytes, Langerhans cells and dendritic cells and has been shown to mediate IgE-dependent allergen presentation To investigate FczRI-mediated cellular events iixthcr we examined whether Fc&RI mediates cytokine production by monocytes and monocyte-derived dendritic cells fMoDC) from wdients with atomic dermatitis (AD) and non-atooic individuals by intracellular cy&ine staining and flowcytometric an&is. The levels of FcERI expression and in viva bound IgE on monocytes from AD patients were significantly higher than those on monocytes from non-atopic donors Cross-linking of Fc&I induced production of IL-6, TNFa, IL-8 monocytes from non-atopic individuals in addition to the spontaneous

and IL-Ip production

by of

these cytokines. Both the levels of spontaneous and F&U-mediated cytokine production were much higher in monocytes from patients with AD compared with non-atopic monocytes. MoDC, obtained by culturing monocytes 4 days in the presence of GM-CSF and IL-4, revealed lower levels of FaRI than monocytes. MoDC both from AD patients and non-atopic IL-6, TNFu, IL-8 producing capacity that monocytes proinflammatory

Frsuke Koch. Karoline H. Zeuter. Andreas c. Hlffner. Gunter Bum. Thomas M. Kiiodi. Department of Dermatology. University Hospital, Ziirich a pmcedum that

combines oral administration of B-MOP. subsequent leukopheresis. extmcorporal UV-A irradiation and reinfusion of PBL back into the patient. Such photochemically altered lymphoma

cells are prewmed

to induca an anti-tumor immune response. Our study

eatabltished a mouse fymphoma mcdel to evaluate this hypothesis. C57BLls mica were immunized with syngeneic photochemically treated lymphoma cells (EL-4). In fad, such immunized mice were protected against subsequent tumor chaHenge. CCM-. CD&

, andT

ceil receptor a deficient knock out mica are used for funher analysis of the immunological effedor mechanisms involved in tumor pmtedion.

and IL-0 after cross-linking of F&U, although their cytokine was much lower than those of monocyies Our results indicate

and dendritic cells amplify inflammatory responses by Fc&RI-mediated cytokine production in atopic disorders and hos! d?hm:3c

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1047 ANIN“I”0MOUSE LYMPHOMA MODEL FOR PHOTOPHERESIS. Cutaneous T cell lymphoma (CTCL) can be treated with phdopiwesis,

on their cell surfaces donors also produce

CYTOKINE EXPRESSION IN A MOUSE MODEL OF EOSINOPHILIC DERMATITIS. Harm HoeenEsch. Sandra E. Torreerosa Dawn&m Boeeess, John P. Sundberg, Department of Veterinary Pathobiology, Purdue University, West Lafayette, Chronic

IN; The Jackson Laboratory, Bar Harbor, ME. proliferative dermatitis (gene symbol: cpdm) is a spontaneous

autosomal

recessive mutation in C57BL/KaLawRij mice. The skin lesions are characterized epidermal hypaplasia, infiltration of the skin with easinophils and macrophages, mast cell hyperplasia, and dermal neovasculmization. Previous studies indicated that the infiltration of the skin by eosinophils is the primary event in the pathogenesis

of the skin lesions.

In order to understand

the mechanisms

by

that play a

role in the eosinophil infiltration in the skin, we determined the expression of cytokines in the skin of 8-10 week old mice by RT-PCR. Little expression of mRNA for the type 2 cytokines IL-l, IL-5, and IL-1 3 was detectable in normal skin. The expression was markedly increased in cpdr&dm skin lesions. There was moderate expression of the mRNA for the chemokines eotaxin and MCPJ in the skin of control mice.

The expression

of eotaxin mRNA was moderately

increased and the expression of MCP-5 mRNA was slightly increased in the affected skin of cpdmkpdm mice. We conclude that increased expression of type 2 cytokines and eotaxin may play a role in the infiltration and survival of eosinophds in the skin of cpdnfcpdm mice.