Allergen dendritic cell

Malefyt R. Meng Q. Kay AB. Phipps S. Lee TH. Ying S Early production of thymic stromal lymphopoie-tin precedes infiltration of dendritic cells expressing its receptor in allergen-induced late phase cutaneous responses in atopic subjects. Allergy 2009 64 1014-1022. 

It is generally accepted (based on clinical and in vitro studies) that mast cells (and basophils), IgE and FceRI are involved in most cases of allergen-induced anaphylaxis in humans. However, it is difficult to define the exact roles and relative importance of mast cells, basophils, and other potential effector cells (e.g monocytes/macrophages, dendritic cells) in either IgE-dependent or IgE-independent human anaphylaxis. Unlike in mice, we neither have access to mast cell- or basophil-deficient humans nor can we genetically manipulate human subjects to produce such phenotypes. 

Rougier, N.et al., In vitro evaluation of the sensitization potential of weak contact allergens using Langerhans-like dendritic cells and autologous T cells, Toxicology, 145, 73, 2000. 

Coutant, K.D. et al., Modulation of the activity of human monocyte-derived dendritic cells by chemical haptens, a metal allergen, and a staphylococcal superantigen, Toxicol. Sci., 52, 189, 1999. 

Atopic dermatitis has been proposed to be the cutaneous manifestation of IgE-mediated hypersensitive reaction to allergenic substances [29]. Conceptually, antagonizing IgE emerges as a logical therapeutic option. Systemic treatment with omalizumab, however, appears to be less efficacious in the skin than in the airway mucosa [23]. It is possible that small molecule Syk inhibitors may offer a more suitable mode to reach and prevent activation of sensitized dermal mast cells and dendritic cells. 

Van Rijt LS. Prins JB, deVries VC, Leenen PJ. Thielemans K, Hoogsteden HC, Lambrecht BN Allergen-induced accumulation of airway dendritic cells is supported by an increase in CD31 Ly-6C hematopoietic precursors. Blood 2002 100 3663-3671. 

Miyahara N, Yang ES, Taube C, Joetham A, Park JW, Dakhama A, Gelfand EW Importance of myeloid dendritic cells in persistent airway disease after repeated allergen exposure. Am J Respir Grit Care Med 2006 173 42-55. 

Upham JW, Denburg JA, O Byrne PM Rapid response of circulating myeloid dendritic cells to inhaled allergen in asthmatic subjects. Clin Exp Allergy 2002 32 818-823. 

Jahnsen FL, Moloney ED, Hogan T, Upham JW, Burke CM, Holt PG Rapid dendritic cell recruitment to the bronchial mucosa of patients with atopic asthma in response to local allergen challenge. Thorax 2001 56 823-826. 

Bratke K, Lommatzsch M, Julius P, Kuepper M, Kleine HD, Luttmann W, Christian Virchow J Dendritic cell subsets in human bronchoalveolar lavage fluid after segmental allergen challenge. Thorax 2007 62 168-175. 

Based on the kno vledge of the processes of T cell sensitization by chemicals and the importance of T cells in induction of autoimmune diseases a number of key indicators of autoimmunogenic compounds can be defined. These include the possibility to be subject of metabolic conversion (either intra- or extra-hepatically), the capacity to activate dendritic cells, to induce cytokine production (in any cell type), or the potency to cause cell stress or cell death. Most of these processes can be studied in vitro, but none of the available methods have been tested for this purpose and often chemicals may behave completely different in vitro than in vivo. However, much can be learned from initiatives to design alternative methods for contact allergens, as many of these basic processes that lead to T cell sensitization are similar for allergenic and autoimmunogenic chemicals. 

De Smedt, A.C., Van Den Heuvel, R.L., Van Tendeloo, V.F., Berneman, Z.N., Schoeters, G.E., Weber, E. and Tuschl, H. (2002) Phenotypic alterations and 11-1 neta production in CD34( +) progenitor- and monocyte-derived dendritic cells after exposure to allergens a comparative analysis. Archives of Dermatological Research, 294, 109-116. 

An intriguing question concerns the immune response elicited by allergen extracts at the mucosal surface. Some studies, in animal models, provided interesting information the dendritic cells of oral mucosa act as efficient antigen-presenting cells and produce IL-12, which directs the immune response towards a Thl profile away from pro-IgE-Th2 profile [6-8],... 

Brand, U., Bellinghausen, I., Enk, A. H. et al. 1999. Allergen specific immune deviation from a Th2 to a Thl response induced by dendritic cells and collagen type. J Allergy Clin Immunol 104 1052-1059. 

Noirey, N., Rougier, N., Andre, C., Schmitt, D., and Vincent, C. 2000. Langerhans-like dendritic cells generated from cord blood progenitors internalize pollen allergens by macro-pinocytosis, and part of the molecules are processed and can activate autologous native T lymphocytes. J Allergy Clin Immunol 105 1194-1201. 

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