SummaryKawasaki disease (KD) is an acute systemic vasculitis of childhood that does not have a known cause or aetiology. The epidemiological features (existence of epidemics, community outbreaks and seasonality), unique age distribution and clinical symptoms and signs of KD suggest that the disease is caused by one or more infectious environmental triggers. However, KD is not transmitted person-to-person and does not occur in clusters within households, schools or nurseries. KD is a self-limited illness that is not associated with the production of autoantibodies or the deposition of immune complexes, and it rarely recurs. Regarding the underlying pathophysiology of KD, innate immune activity (the inflammasome) is believed to play a role in the development of KD vasculitis, based on the results of studies with animal models and the clinical and laboratory findings of KD patients. Animal studies have demonstrated that innate immune pathogen-associated molecular patterns (PAMPs) can cause vasculitis independently of acquired immunity and have provided valuable insights regarding the underlying mechanisms of this phenomenon. To validate this concept, we recently searched for KD-specific PAMPs and identified such molecules with high specificity and sensitivity. These molecules have structures similar to those of microbe-associated molecular patterns (MAMPs), as shown by liquid chromatography-tandem mass spectrometry. We propose herein that KD is an innate immune disorder resulting from the exposure of a genetically predisposed individual to microbe-derived innate immune stimulants and that it is not a typical infectious disease.

Phosphatidyl-inositol mannosides (PIM) are glycolipids unique to mycobacteria and other related bacteria that stimulate host immune responses and are implicated in mycobacteria pathogenicity. Here, we found that the FcRγ-coupled C-type lectin receptor DCAR (dendritic cell immunoactivating receptor; gene symbol Clec4b1) is a direct receptor for PIM. Mycobacteria activated reporter cells expressing DCAR, and delipidation of mycobacteria abolished this activity. Acylated PIMs purified from mycobacteria were identified as ligands for DCAR. DCAR was predominantly expressed in small peritoneal macrophages and monocyte-derived inflammatory cells in lungs and spleen. These cells produced monocyte chemoattractant protein-1 (MCP-1) upon PIM treatment, and absence of DCAR or FcRγ abrogated MCP-1 production. Upon mycobacterial infection, Clec4b1-deficient mice showed reduced numbers of monocyte-derived inflammatory cells at the infection site, impaired IFNγ production by T cells, and an increased bacterial load. Thus, DCAR is a critical receptor for PIM that functions to promote T cell responses against mycobacteria.

Abstract-The structural states of sodic plagioclase crystals of -50 pm in size from three H6, two L6, and one LL6 chondritic meteorites have been determined by measuring the A131 parameter with a Gandolfi camera after analyzing chemical compositions. The temperature for each sodic plagioclase crystal has been determined by plotting the A1 3 1 parameter, corrected for the influence of K, on the relation diagram between the A 13 1 parameter and the temperature of synthesis of sodic plagioclase by Smith (1972). The temperature obtained is assigned to the crystallization temperature of sodic plagioclase, and the maximum plagioclase temperature for each meteorite can be assumed to correspond to the maximum temperature attained by each meteorite during metamorphism. The maximum metamorphic temperatures estimated are 725-742 "C for the H6 chondrites, 808-820 "C for the L6 chondrites, and 800 "C for the LL6 chondrite. These temperatures are lower than those based on Ca contents of clinopyroxenes (Dodd, 1981;McSween et al., 1988) but are consistent with those based on Ca contents of orthopyroxenes (McSween and Patchen, 1989;Langenhorst et al., 1995;Jones, 1997). The K content of sodic plagioclase correlates with the temperature obtained from the structural state. This positive correlation suggests that sodic plagioclase has formed in the course of equilibration processes of alkali elements in prograde metamorphism ( i e., during heating processes). The results of this study (Le., the maximum metamorphic temperature of the H6 chondrites is lower than that of the L6 chondrites by -80 "C, and meteorites of the same chemical group show very similar maximum metamorphic temperatures) are in accordance with the predictions of calculations based on the 26Al heat source and the onion-shell structure model of the parent bodies.

Objective— Nod1 is an intracellular pattern recognition receptor for bacterial peptidoglycan fragments. We previously reported that a synthetic Nod1 ligand, FK565, induced acute coronary arteritis in mice similar to that of Kawasaki disease. However, the molecular mechanisms underlying this characteristic inflammation have remained elusive. Approach and Results— We found that CD11c + MHC class II + cells accumulated in the heart of FK565-treated mice before arteritis development. Morphological features and gene expression signatures of the cardiac CD11c + MHC class II + cells suggested that this population is closely related to macrophages, and thus, we designated them cardiac CD11c + macrophages. Nod1 in nonhematopoietic cells, rather than hematopoietic cells, was required for the increase of cardiac CD11c + macrophages and arteritis development. Among nonhematopoietic cells, cardiac endothelial cells produced a large amount of chemokines in response to FK565. Endothelial cell–specific blockade of Nod1 signaling suppressed FK565-induced expression of these chemokines, accumulation of cardiac CD11c + macrophages, and subsequent coronary arteritis development. We also found that CCR2 + Ly6C hi inflammatory monocytes in peripheral blood supplied precursors of cardiac CD11c + macrophages. CCR2-deficient mice or pertussis toxin–treated mice exhibited decreased numbers of cardiac CD11c + macrophages and reduced arteritis. Conclusions— These results suggest that Ly6C hi monocytes are recruited to FK565-activated endothelial cells to generate cardiac CD11c + macrophages, which play a pivotal role in the pathogenesis of acute coronary arteritis.