Mucosal Immunity and Sublingual Immunotherapy in Respiratory Disorders
1Division of Pediatric Allergy, Immunology and Pulmonology, Near East University Hospital, Nicosia, Cyprus
2Division of Pediatric Allergy and Immunology, Cukurova University Hospital, Adana, Turkey
3Section of Allergy and Clinical Immunology, Imperial College London, UK
Mucosal Immunity and Sublingual Immunotherapy in Respiratory Disorders
Description
Delivery of allergens through mucosal routes as an alternative to subcutaneous immunotherapy (IT) in allergic airway disease has been proposed. The sublingual mucosa belongs to the sophisticated network of mucosal immune system, where tolerance induction towards a variety of antigens from commensal bacterial and nutritional products predominates to maintain local immunostasis. Oral mucosal tissue displays high permeability also for allergens, and orally applied allergen had been shown to retain within oral tissue up to 20 hours. Most likely Langerhans-like local dendritic cells (DCs) are critically involved in this process. During sublingual mucosal IT, the allergen is captured within the oral mucosa by Langerhans-like DCs, and subsequently DCs mature and migrate to proximal draining lymph nodes where production of blocking IgG antibodies and the induction of T lymphocytes with suppressive function take place. Oral mucosal Langerhans cells (oLCs) differ from the classical epidermal LCs, especially by the constitutive expression of the high-affinity receptor for IgE. Moreover oLCs exhibit high expression of major histocompatibility complex class I and II, as well as, costimulatory molecules (CD40, CD80/B7.1, and CD86/B7.2) which may suggest the specific function of these cells within the regional immune system of the oral mucosa. Activation of Toll-like receptor (TLR) 4 on oLC by monophosphoryl A led to an upregulation of coinhibitory molecules B7-H1 and B7-H3 as well as to the induction of IL-10 production by oLCs. Furthermore, ligation of TLR4 on human oLC induced Foxp3 (+) Tregs producing IL-10 and TGF-β1 next to IFN-γ producing Th1 cells. This leads to the assumption that innate immune receptors such as TLR4 on human oLC are involved in the maintenance of natural tolerance within oral mucosal tissue.
Oral mucosal DCs as targets for adjuvants in sublingual immunotherapy (SLIT) open the questions whether TLR ligands could enhance the efficiency of SLIT. Adjuvants such as synthetic pseudo-di-peptide molecule OM-294-BA-MP or a combination of 1, 25-dihydroxyvitamin D3 and dexamethasone provided promising results. Understanding of the interaction of allergen and oLCs may allow improved targeting of SLIT vaccines. In the new future, combination of allergen products with adjuvants may improve efficacy of IT via the sublingual route. Potential topics include, but are not limited to:
- Recent developments in oral Langerhans-like DCs
- Mechanisms of tolerance induction in the sublingual tissue
- New developments in allergens (recombinant, peptide, and tablet forms) in SLIT
- Optimal allergen dose for tolerance induction
- Use of adjuvants
- Long-term benefits of SLIT
Before submission authors should carefully read over the journal's Author Guidelines, which are located at http://www.hindawi.com/journals/ja/guidelines/. Prospective authors should submit an electronic copy of their complete manuscript through the journal Manuscript Tracking System at http://mts.hindawi.com/ according to the following timetable: