Efficient drug delivery to lymph nodes by intradermal administration and enhancement of anti-tumor effects of immune checkpoint inhibitors.

Immune checkpoint inhibitors are novel immunotherapy drugs that have improved cancer treatments. Yet only a small percentage of patients experience durable responses to immune checkpoint inhibitors. Recently, it has been suggested that lymph nodes are important for the efficacy of immunotherapy.

Dose-sparing effect of Sabin-derived inactivated polio vaccine produced in Japan by intradermal injection device for rats.

The live-attenuated oral polio vaccine has long been used as the standard for polio prevention, but in order to minimize the emergence of pathogenic revertants, the inactivated polio vaccine (IPV), which is administered intramuscularly or subcutaneously, is being increasingly demanded worldwide. However, there is a global shortage of IPV, and its cost is an obstacle in developing countries. Therefore, dose-sparing with intradermal administration of IPV has been investigated.

Performance and usability evaluation of novel intradermal injection device Immucise™ and reanalysis of intradermal administration trials of influenza vaccine for the elderly.

Under the pandemic situation, there is an urgent need to produce and acquire sufficient quantities of prophylactic vaccines. It becomes important to devise a way to achieve reliable immunity with lower doses to distribute limited supplies of vaccines to maximum number of people very quickly. Intradermal (ID) vaccination is one such method to increase the effectiveness of vaccines.

Identification of 20-hydroxyecdysone-inducible genes from larval brain of the silkworm, Bombyx mori, and their expression analysis.

The insect brain secretes prothoracicotropic hormone (PTTH), which stimulates the prothoracic gland to synthesize ecdysone. The active metabolite of ecdysone, 20-hydroxyecdysone (20E), works through ecdysone receptor (EcR) and ultraspiracle (USP) to initiate molting and metamorphosis by regulating downstream genes. Previously, we found that EcR was expressed in the PTTH-producing neurosecretory cells (PTPCs) in larval brain of the silkworm Bombyx mori, suggesting that PTPCs function as the master cells of development under the regulation of 20E.

Expression of 20-hydroxyecdysone-induced genes in the silkworm brain and their functional analysis in post-embryonic development.

The insect brain is the center of developmental control, from which ecdysone governs brain morphogenesis and regulates gene expression cascades associated with molting and metamorphosis. In order to identify the 20-hydroxyecdysone (20E)-inducible genes responsible for molting and metamorphosis, we constructed a 20E-induced subtraction complementary DNA library from the fifth instar larval brain of the silkworm Bombyx mori. We isolated 10 genes, designated as bombeil-1 to bombeil-10, three of which did not show any sequence similarity to previously identified Bombyx genes.

Deficiency in EBV-induced gene 3 (EBI3) in MRL/lpr mice results in pathological alteration of autoimmune glomerulonephritis and sialadenitis.

MRL/lpr mice develop a systemic autoimmune disease that is reminiscent of systemic lupus erythematosus (SLE) and Sjögren's syndrome in humans. To investigate the role of IL-27 in the development of autoimmune disorders in MRL/lpr mice, we disrupted the EBV-induced gene 3 (EBI3), which is a subunit of IL-27. Consequently, the pathophysiology of glomerulonephritis and sialadenitis, which develops in MRL/lpr mice, was drastically changed.

EcR expression in the prothoracicotropic hormone-producing neurosecretory cells of the Bombyx mori brain.

The steroid hormone 20-hydroxyecdysone (20E) initiates insect molting and metamorphosis through binding with a heterodimer of two nuclear receptors, the ecdysone receptor (EcR) and ultraspiracle (USP). Expression of the specific isoforms EcR-A and EcR-B1 governs steroid-induced responses in the developing cells of the silkworm Bombyx mori. Here, analysis of EcR-A and EcR-B1 expression during larval-pupal development showed that both genes were up-regulated by 20E in the B.

Amelioration of autoimmune nephritis by imatinib in MRL/lpr mice.

Objective: To examine whether the platelet-derived growth factor (PDGF) receptor antagonist imatinib ameliorates glomerulonephritis in MRL/lpr mice, a condition that is similar to severe lupus nephritis in humans.

Methods: Sixteen-week-old MRL/lpr female mice having an advanced stage of glomerulonephritis were divided into 3 groups according to treatment: 1) 50 mg/kg or 2) 10 mg/kg of imatinib (administered orally 4 times a week up to 24 weeks of age) or 3) vehicle solution (untreated group). The histopathologic condition of the kidneys and salivary glands of each mouse as well as the cumulative survival rates, extent of lymphadenopathy and splenomegaly, and serum chemistry and immunologic values were assessed.

Membranous glomerulonephritis development with Th2-type immune deviations in MRL/lpr mice deficient for IL-27 receptor (WSX-1).

MRL/lpr mice develop spontaneous glomerulonephritis that is essentially identical with diffuse proliferative glomerulonephritis (World Health Organization class IV) in human lupus nephritis. Lupus nephritis is one of the most serious complications of systemic lupus erythematosus. Diffuse proliferative glomerulonephritis is associated with autoimmune responses dominated by Th1 cells producing high levels of IFN-gamma.

Association between IFNA genotype and the risk of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterized by multisystem inflammation and production of autoantibodies, which can generate immune complexes and may cause tissue damage through the recognition of an autoantigen. Although many factors have been proposed, such as genetic factors, environmental factors, hormonal action, viruses, and dysregulation of cytokine production, the cause of this disease is not well understood. It has been reported that the levels of interferon (IFN)-alpha in the sera of some SLE patients are elevated and that IFN-alpha induces maturation of monocytes into highly active antigen-presenting dendritic cells (DCs).

Novel regulatory mechanisms of CD40-induced prostanoid synthesis by IL-4 and IL-10 in human monocytes.

Interleukins IL-4 and IL-10 are considered to be central regulators for the limitation and eventual termination of inflammatory responses in vivo, based on their potent anti-inflammatory effects toward LPS-stimulated monocytes/macrophages and neutrophils. However, their role in T cell-dependent inflammatory responses has not been fully elucidated. In this study, we investigated the effects of both cytokines on the production of PGE(2), a key molecule of various inflammatory conditions, in CD40-stimulated human peripheral blood monocytes.

Influence of interleukin-12 receptor beta1 polymorphisms on tuberculosis.

Host genetic factors may be important determinants of susceptibility to tuberculosis, and several candidate gene polymorphisms have been shown to date. A series of recent reports concerning rare human deficiencies in the type-1 cytokine pathway suggest that more subtle variants of relevant genes may also contribute to susceptibility to tuberculosis at the general population level. To investigate whether polymorphisms in the interleukin-12 receptor (IL-12R) gene predispose individuals to tuberculosis, we studied these genes by single-strand conformational polymorphism analysis and direct sequencing.