PMID- 18947863 OWN - NLM STAT- MEDLINE DCOM- 20090127 LR - 20210409 IS - 1097-6825 (Electronic) IS - 0091-6749 (Linking) VI - 123 IP - 1 DP - 2009 Jan TI - Allergen-enhanced thrombomodulin (blood dendritic cell antigen 3, CD141) expression on dendritic cells is associated with a TH2-skewed immune response. PG - 209-216.e4 LID - 10.1016/j.jaci.2008.09.009 [doi] AB - BACKGROUND: Dendritic cells (DCs) are important in allergic diseases such as asthma, although little is known regarding the mechanisms by which DCs induce T(H)2-polarized responses in atopic individuals. It has been suggested that intrinsic properties of allergens can directly stimulate T(H)2 polarizing functions of DCs, but little is known of the underlying mechanisms. OBJECTIVE: To identify novel genes expressed by house dust mite (HDM) allergen-exposed DCs. METHODS: We screened for allergen-induced gene expression by microarray, and validated differentially expressed genes at the mRNA and protein levels. RESULTS: Thrombomodulin (CD141, blood dendritic cell antigen 3) expression by microarray was higher on HDM-stimulated DCs from atopic (relative to nonatopic) individuals. These findings were confirmed at both the mRNA and protein levels in an independent group. Purified thrombomodulin(+) DCs induced a strongly T(H)2-polarized cytokine response by allergen-specific T cells compared with DCs lacking thrombomodulin. In vivo, thrombomodulin(+) circulating DCs were significantly more frequent in subjects with HDM allergy and asthma, compared with control subjects. Furthermore, thrombomodulin expression in blood leukocytes was higher in children with acute asthma than at convalescence 6 weeks later. CONCLUSION: Thrombomodulin expression on DCs may be involved in the pathogenesis of atopy and asthma. FAU - Yerkovich, Stephanie T AU - Yerkovich ST AD - Telethon Institute for Child Health Research, Centre for Child Health Research, Faculty of Medicine and Dentistry, University of Western Australia, Perth, Australia. FAU - Roponen, Marjut AU - Roponen M FAU - Smith, Miranda E AU - Smith ME FAU - McKenna, Kathy AU - McKenna K FAU - Bosco, Anthony AU - Bosco A FAU - Subrata, Lily S AU - Subrata LS FAU - Mamessier, Emilie AU - Mamessier E FAU - Wikstrom, Matthew E AU - Wikstrom ME FAU - Le Souef, Peter AU - Le Souef P FAU - Sly, Peter D AU - Sly PD FAU - Holt, Patrick G AU - Holt PG FAU - Upham, John W AU - Upham JW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20081022 PL - United States TA - J Allergy Clin Immunol JT - The Journal of allergy and clinical immunology JID - 1275002 RN - 0 (Antigens, Dermatophagoides) RN - 0 (Antigens, Surface) RN - 0 (THBD protein, human) RN - 0 (Thrombomodulin) SB - IM CIN - J Allergy Clin Immunol. 2009 May;123(5):1192; author reply 1192-3. PMID: 19251314 MH - Adolescent MH - Adult MH - Aged MH - Antigens, Dermatophagoides/*immunology/pharmacology MH - Antigens, Surface/biosynthesis/*immunology MH - Asthma/*immunology/metabolism/pathology MH - Child MH - Child, Preschool MH - Convalescence MH - Dendritic Cells/*immunology/metabolism/*pathology MH - Female MH - Gene Expression Profiling/methods MH - Gene Expression Regulation/drug effects/immunology MH - Humans MH - Male MH - Middle Aged MH - Oligonucleotide Array Sequence Analysis/methods MH - Th2 Cells/*immunology/pathology MH - Thrombomodulin/biosynthesis/*immunology EDAT- 2008/10/25 09:00 MHDA- 2009/01/28 09:00 CRDT- 2008/10/25 09:00 PHST- 2008/01/30 00:00 [received] PHST- 2008/09/03 00:00 [revised] PHST- 2008/09/05 00:00 [accepted] PHST- 2008/10/25 09:00 [pubmed] PHST- 2009/01/28 09:00 [medline] PHST- 2008/10/25 09:00 [entrez] AID - S0091-6749(08)01670-9 [pii] AID - 10.1016/j.jaci.2008.09.009 [doi] PST - ppublish SO - J Allergy Clin Immunol. 2009 Jan;123(1):209-216.e4. doi: 10.1016/j.jaci.2008.09.009. Epub 2008 Oct 22.