Craniofacial mucosal immune system: importance of its unique organogenesis and function in the development of a mucosal vaccine.

Mucosa-associated lymphoid tissues (MALT) play a critical role as inductive sites for the initiation of antigen-specific protective immunity against pathogens penetrating the mucus membranes. Nasopharynx-associated lymphoid tissue (NALT), situated at the bottom of the rodent nasal cavity, is thought to be an important site for the induction of antigen-specific immune response to inhaled antigens. In addition, we have recently shown that tear duct-associated lymphoid tissue (TALT), present in the murine tear duct bridging the ocular and nasal cavities, is involved in the induction and regulation of both nasal and ocular immunity. Interestingly, cellular requirements for the organogenesis of NALT and TALT are quite different from those of other MALT (e.g. Peyer's patches; PPs) and peripheral lymphoid tissues. Moreover, mucosal imprinting molecules of NALT and TALT inducer cells are totally independent of currently known chemokines and adhesion molecules in PPs and lymph nodes, such as the CXCR5-CXCL13, α4β1 integrin-vascular cell adhesion molecule-1 (VCAM1), and CCR9-CCL25 axes. NALT and TALT lymphocytes are also independent of these tissue-specific migration molecules. Together with already-characterized conjunctiva-associated lymphoid tissue (CALT ), which has been demonstrated to play a critical role in ocular defense, the MALT associated with the head region seems to be coordinately organizing the unique craniofacial mucosal immune system of the ocular, nasal, oral-pharynx mucus membranes. Clarification of the immunological network of this unique craniofacial immune system will facilitate the development of a safe and effective mucosal vaccine against respiratory and ocular infections.