PMID- 19400908 OWN - NLM STAT- MEDLINE DCOM- 20090826 LR - 20221207 IS - 1365-2222 (Electronic) IS - 0954-7894 (Print) IS - 0954-7894 (Linking) VI - 39 IP - 6 DP - 2009 Jun TI - Thymic stromal lymphopoietin, OX40-ligand, and interleukin-25 in allergic responses. PG - 798-806 LID - 10.1111/j.1365-2222.2009.03241.x [doi] AB - Allergic diseases are often triggered by environmental allergens that induce dominant type 2 immune responses, characterized by the infiltrated T-helper type 2 (TH2) lymphocytes, eosinophils, and elevated TH2 cytokines. In addition to TH2 type immune responses, epithelial stress and injury linked to tissue remodelling are often observed, suggesting that epithelial cells may play important role in regulating allergic responses. Dendritic cells (DCs), the professional antigen-presenting cells with the capabilities of sampling allergens, are considered as the key player on instructing TH2 immune responses. Whether inflamed epithelium can regulate innate immunity, such as macrophages and DCs, which in turn instructs adaptive immunity has long been hypothesized. Studies of thymic stromal lymphopoietin (TSLP), an epithelial cells-derived cytokine, that can strongly activate DCs, provide important evidences that the epithelial barrier can trigger allergic diseases by regulating immune responses. The finding that OX40/OX40Ligand (OX40L) interactions are the molecular trigger responsible for the induction and maintenance of TH2 responses by TSLP-activated DCs provides a plausible molecular explanation for TSLP-mediated allergy. Recent progresses in characterizing the pro-inflammatory IL-17 cytokine family have added an additional layer of complexity on the regulation of allergic inflammation. TSLP-DCs can induce a robust expansion of TH2 memory cells and strengthen functional attributes by up-regulating their surface expression of IL-17RB (IL-25R), the receptor for cytokine IL-17E (IL-25), a distinct member of IL-17 cytokine family. IL-17E (also known as IL-25) produced by epithelial cells, and other innate cells, such as eosinphils, basophils, and mast cells, are shown to regulate adaptive immunity by enhancing TH2 cytokine productions. These exciting findings expand our knowledge of the complex immunological cascades that result in allergic inflammation and may provide novel therapeutic approaches for the treatment of allergic diseases. FAU - Wang, Y-H AU - Wang YH AD - Department of Immunology and Center of Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. yui_hsi.wang@cchmc.org FAU - Liu, Y-J AU - Liu YJ LA - eng GR - R01 AI061645/AI/NIAID NIH HHS/United States GR - R01 AI061645-05/AI/NIAID NIH HHS/United States PT - Journal Article PT - Review DEP - 20090407 PL - England TA - Clin Exp Allergy JT - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JID - 8906443 RN - 0 (CRLF2 protein, human) RN - 0 (Cytokines) RN - 0 (Immunoglobulins) RN - 0 (Interleukin-17) RN - 0 (OX40 Ligand) RN - 0 (Receptors, Cytokine) RN - 0 (Tslpr protein, mouse) RN - GT0IL38SP4 (Thymic Stromal Lymphopoietin) SB - IM MH - Animals MH - Cytokines/*immunology/metabolism MH - Dendritic Cells/*immunology/metabolism MH - Epithelial Cells/*immunology/metabolism MH - Humans MH - Hypersensitivity/*immunology/metabolism MH - Immunity, Active MH - Immunity, Innate MH - Immunoglobulins MH - Interleukin-17/*immunology/metabolism MH - OX40 Ligand/*immunology/metabolism MH - Receptors, Cytokine/immunology/metabolism MH - Th2 Cells/immunology/metabolism MH - Thymic Stromal Lymphopoietin PMC - PMC2744577 MID - NIHMS126058 EDAT- 2009/04/30 09:00 MHDA- 2009/08/27 09:00 PMCR- 2010/06/01 CRDT- 2009/04/30 09:00 PHST- 2009/04/30 09:00 [entrez] PHST- 2009/04/30 09:00 [pubmed] PHST- 2009/08/27 09:00 [medline] PHST- 2010/06/01 00:00 [pmc-release] AID - CEA3241 [pii] AID - 10.1111/j.1365-2222.2009.03241.x [doi] PST - ppublish SO - Clin Exp Allergy. 2009 Jun;39(6):798-806. doi: 10.1111/j.1365-2222.2009.03241.x. Epub 2009 Apr 7.