Kaoru Takamura

Cutting edge: Uniqueness of lymphoid chemokine requirement for the initiation and maturation of nasopharynx-associated lymphoid tissue organogenesis.

CD3−CD4+CD45+ inducer cells are required for the initiation of mucosa-associated organogenesis of both nasopharynx-associated lymphoid tissues (NALT) and Peyer’s patches (PP) in the aerodigestive tract. CXCL13−/− mice and mice carrying the paucity of lymph node T cell (plt) mutation and lacking expression of CCL19 and CCL21 accumulate CD3−CD4+CD45+ cells at the site of NALT but not of PP genesis. Although NALT was observed to develop in adult CXCL13−/− and plt/plt mice, the formation of germinal centers in CXCL13−/− mice was affected, and their population of B cells was much lower than in the NALT of CXCL13+/− mice. Similarly, fewer T cells were observed in the NALT of plt/plt mice than in control mice. These findings indicate that the initiation of NALT organogenesis is independent of CXCL13, CCL19, and CCL21. However, the expression of these lymphoid chemokines is essential for the maturation of NALT microarchitecture.

Regulatory Role of Lymphoid Chemokine CCL19 and CCL21 in the Control of Allergic Rhinitis

The lymphoid chemokines CCL19 and CCL21 are known to be crucial both for lymphoid cell trafficking and for the structural organization of lymphoid tissues such as nasopharynx-associated lymphoid tissue (NALT). However, their role in allergic responses remains unclear, and so our current study aims to shed light on the role of CCL19/CCL21 in the development of allergic rhinitis. After nasal challenge with OVA, OVA-sensitized plt (paucity of lymph node T cells) mice, which are deficient in CCL19/CCL21, showed more severe allergic symptoms than did identically treated wild-type mice. OVA-specific IgE production, eosinophil infiltration, and Th2 responses were enhanced in the upper airway of plt mice. Moreover, in plt mice, the number of CD4+CD25+ regulatory T cells declined in the secondary lymphoid tissues, whereas the number of Th2-inducer-type CD8α−CD11b+ myeloid dendritic cells (m-DCs) increased in cervical lymph nodes and NALT. Nasal administration of the plasmid-encoding DNA of CCL19 resulted in the reduction of m-DCs in the secondary lymphoid tissues and the suppression of allergic responses in plt mice. These results suggest that CCL19/CCL21 act as regulatory chemokines for the control of airway allergic disease and so may offer a new strategy for the control of allergic disease.

Efficient induction of oral tolerance by fusing cholera toxin B subunit with allergen-specific T-cell epitopes accumulated in rice seed.

Cholera toxin B (CTB) subunit is an efficient mucosal carrier molecule for induction of oral tolerance to antigens and allergens. Here, T-cell epitopes of Cry j 1 and Cry j 2, major allergens in Japanese cedar pollen, were expressed in rice seed as a fusion protein with either CTB or rice glutelin as a control. Feeding mice with rice seed containing CTB-fused T-cell epitopes suppressed allergen-specific IgE responses and pollen-induced clinical symptoms at 50-fold lower doses of T-cell epitopes than required when using control seed. Our findings present a novel potential strategy for immunotherapy of type-I allergy.

Implications of nasopharynx-associated lymphoid tissue (NALT) in the development of allergic responses in an allergic rhinitis mouse model

Nasopharynx‐associated lymphoid tissue (NALT) serves as an important inductive site for mucosal immunity in the upper respiratory tract. Despite its importance in the mucosal immune system, little is known regarding the role of NALT in airway allergic immune responses. We aimed to elucidate the role of NALT in the induction of upper airway allergic responses in a mouse model.

Role of interleukin-15 in the development of mouse olfactory nerve

Interleukin (IL)‐15 interacts with components of the IL‐2 receptor (R) and exhibits T cell‐stimulating activity similar to that of IL‐2. In addition, IL‐15 is widely expressed in many cell types and tissues, including the central nervous system. We provide evidence of a novel role of IL‐15 in olfactory neurogenesis. Both IL‐15 and IL‐15Rα were expressed in neuronal precursor cells of the developing olfactory epithelium in mice. Adult IL‐15Rα knockout mice had fewer mature olfactory neurons and proliferating cells than wild‐type. Our results suggest that IL‐15 plays an important role in regulating cell proliferation in olfactory neurogenesis.