Subcutaneous Versus Sublingual Immunotherapy for Allergic Rhinitis and/or Asthma

Nerin Nadir Bahceciler; Nazan Cobanoglu


Immunotherapy. 2011;3(6):747-756. 

In This Article

Oral Mucosal Immune Responses

It is postulated that Langerhans-like local DCs are most likely to be critically involved in the persistence of allergen in the sublingual area.[68] One explanation for the success of SLIT is the profound difference between oral Langerhans cells (LCs) and their skin counterparts. LCs represent the predominating DC population within human oral mucosa, whereas plasmacytoid DCs (pDCs) are virtually absent.[95,96] Nevertheless, oral mucosal LCs (oLCs) differ from the classical epidermal LCs (eLCs), especially by the constitutive expression of the high-affinity receptor for IgE (FcεRI).[96,97] FcεRI appears in early differentiation of LCs, leading to the suggestion that oLCs represent a more immature DC subpopulation, which would further underline their pro-tolerogenic character.[98] oLCs are located within the suprabasal epithelium layer, it is most likely that they bind and process allergens during SLIT. Moreover, oLCs exhibit high expression of MHC 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.[99] Activation of Toll-like receptor (TLR)4 on oLCs by monophosphoryl A (MPL) led to an upregulation of coinhibitory molecules B7-H1 and B7-H3 as well as to the induction of IL-10 production by oLCs.[100] Furthermore, ligation of TLR4 on human oLCs induced Foxp3+ Tregs to produce IL-10 and TGF-β1 near IFN-γ-producing Th1 cells.[100] This leads to the assumption that innate immune receptors such as TLR4 on human oLCs are involved in the maintenance of natural tolerance within oral mucosal tissue.

Oral mucosal DCs as targets for adjuvants in SLIT raises the questions of whether TLR ligands could enhance the efficiency of SLIT. Recently, it has been demonstrated in a BALB/c asthma model that TLR2 activation via Pam3CSK4 together with ovalbumin (OVA) decreased airway hyper-responsiveness and Th2 responses in the cervical lymph node of mice previously sensitized to OVA along with the upregulation of IL-10 and the induction of IFN-γ- and IL-10-producing T cells in oral mucosal DCs.[101] Other adjuvants such as synthetic pseudodipeptide molecule OM-294-BA-MP or a combination of 1,25-dihydroxyvitamin D3 and dexamethasone (VitD3/Dex) provided similar results.[102,103] Murine oral DCs could also be formed by mucoadhesive formulations such as chitosan particles, which facilitate allergen contact to oral mucosa leading to increased induction of IFN-γ- and IL-10-producing T cells.[104]


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