Cover
(Source: International Immunology)
Source: International Immunology - March 23, 2015 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research

Drak2 is not required for tumor surveillance and suppression
Drak2 is a promising therapeutic target to treat organ-specific autoimmune diseases such as type 1 diabetes and multiple sclerosis without causing generalized immune suppression. Inhibition of Drak2 may also prevent graft rejection following organ transplantation. However, Drak2 may function as a critical tumor suppressor, which would challenge the prospect of targeting Drak2 for therapeutic treatment. Thus, we examined the susceptibility of Drak2 –/– mice in several tumor models. We show that Drak2 is not required to prevent tumor formation in a variety of settings. Therefore, Drak2 does not function as an es...
Source: International Immunology - February 19, 2015 Category: Allergy & Immunology Authors: Edwards, B. A., Harris, T. L., Floersh, H., Lukens, J. R., Zaki, M. H., Vogel, P., Kanneganti, T.-D., Bui, J. D., McGargill, M. A. Tags: Short communication Source Type: research

The differential characterization of GPR55 receptor in human peripheral blood reveals a distinctive expression in monocytes and NK cells and a proinflammatory role in these innate cells
G protein-coupled receptor 55 (GPR55) is activated by endogenous, plant-derived and synthetic cannabinoids. Recent studies reported a broad tissue distribution for GPR55 and found prominent roles for this receptor in inflammatory pain, gut and bone physiology, as well as cancer. However, little is known about the expression and function of GPR55 in immune cells. To address this question, we performed a detailed characterization of GPR55 in different human innate and adaptive immune populations using polychromatic flow cytometry and we found that monocytes and NK cells expressed remarkable levels of this receptor compared t...
Source: International Immunology - February 19, 2015 Category: Allergy & Immunology Authors: Chiurchiu, V., Lanuti, M., De Bardi, M., Battistini, L., Maccarrone, M. Tags: Original Research Source Type: research

A novel function of interferon regulatory factor-1: inhibition of Th2 cells by down-regulating the Il4 gene during Listeria infection
Infection with certain pathogens induces a shift of the Th subset balance to a Th1 dominant state. This, in turn, results in the suppression of Th2 responses. We focused on the involvement of interferon regulatory factor-1 (IRF-1) in the suppression of Th2 cells during Listeria infection. We found that the inhibition of IL-4 production by Th2 cells is mediated by a soluble factor (LmSN) produced by Listeria-infected antigen-presenting cells. The inhibition is not observed with T cells from Irf1 gene-targeted mice. IRF-1 suppresses transcription of the Il4 gene in Th2 cells. Under the influence of the LmSN, IRF-1 binds to t...
Source: International Immunology - February 19, 2015 Category: Allergy & Immunology Authors: Maruyama, S., Kanoh, M., Matsumoto, A., Kuwahara, M., Yamashita, M., Asano, Y. Tags: featured content Source Type: research

IL-10 enhances the phenotype of M2 macrophages induced by IL-4 and confers the ability to increase eosinophil migration
In this study, we showed that IL-10 enhanced IL-4Rα expression in M-CSF-induced bone marrow-derived macrophages (BMDMs). Global gene expression analysis of M2 macrophages induced by IL-4, IL-10 or IL-4 + IL-10 showed that IL-10 enhanced gene expression of M2a markers induced by IL-4 in M-CSF-induced BMDMs. Moreover, IL-4 and IL-10 synergistically induced CCL24 (Eotaxin-2) production. Enhanced CCL24 expression was also observed in GM-CSF-induced BMDMs and zymosan-elicited, thioglycolate-elicited and naive peritoneal macrophages. CCL24 is a CCR3 agonist and an eosinophil chemoattractant. In vitro, IL-4 + IL-10-stimulat...
Source: International Immunology - February 19, 2015 Category: Allergy & Immunology Authors: Makita, N., Hizukuri, Y., Yamashiro, K., Murakawa, M., Hayashi, Y. Tags: Original Research Source Type: research

Disease origin and progression in amyotrophic lateral sclerosis: an immunology perspective
The immune system is inextricably linked with many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), a devastating neuromuscular disorder affecting motor cell function with an average survival of 3 years from symptoms onset. In ALS, there is a dynamic interplay between the resident innate immune cells, that is, microglia and astrocytes, which may become progressively harmful to motor neurons. Although innate and adaptive immune responses are associated with progressive neurodegeneration, in the early stages of ALS immune activation pathways are primarily considered to be beneficial promoting neurona...
Source: International Immunology - February 19, 2015 Category: Allergy & Immunology Authors: Malaspina, A., Puentes, F., Amor, S. Tags: Invited review Source Type: research

In This Issue
(Source: International Immunology)
Source: International Immunology - February 19, 2015 Category: Allergy & Immunology Tags: In This Issue Source Type: research

Table of Contents
(Source: International Immunology)
Source: International Immunology - February 19, 2015 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research

Subscriptions
(Source: International Immunology)
Source: International Immunology - February 19, 2015 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research

Cover
(Source: International Immunology)
Source: International Immunology - February 19, 2015 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research

Establishment of a vascular endothelial cell-reactive type II NKT cell clone from a rat model of autoimmune vasculitis
In this study, a T cell clone reactive with rat vascular endothelial cells (REC) was established and named VASC-1. Intravenous injection of VASC-1 induced SVV in normal recipients. VASC-1 was a TCRαβ/CD3-positive CD4/CD8 double-negative T cell clone with expression of NKG2D. The cytokine mRNA profile under unstimulated condition was positive for IL-4 and IFN- but negative for IL-2 and IL-10. After interaction with REC, the mRNA expression of IL-2, IL-5 and IL-6 was induced in VASC-1, which was inhibited by blocking of CD1d on the REC surface. Although the protein levels of these cytokines seemed to be lower than...
Source: International Immunology - January 22, 2015 Category: Allergy & Immunology Authors: Iinuma, C., Waki, M., Kawakami, A., Yamaguchi, M., Tomaru, U., Sasaki, N., Masuda, S., Matsui, Y., Iwasaki, S., Baba, T., Kasahara, M., Yoshiki, T., Paletta, D., Herrmann, T., Ishizu, A. Tags: Original Research Source Type: research

CD72 negatively regulates mouse mast cell functions and down-regulates the expression of KIT and Fc{varepsilon}RI{alpha}
CD72 is a transmembrane protein belonging to the C-type lectin family that is expressed by various hematopoietic cells. When bound to its natural ligand, CD100 (semaphorin 4D), CD72 inhibits the KIT-mediated responses of human mast cells, but not IgE/FcRI-mediated mast cell degranulation. We extended these findings to examine the role of CD72 in mouse mast cells. CD72 expression was detected in mouse bone marrow-derived mast cells (mBMMCs). As for human mast cells, an agonistic antibody against CD72 (K10.6) suppressed the KIT-mediated cell growth of, IL-6 production by and chemotaxis of mBMMCs. However, in contrast to huma...
Source: International Immunology - January 22, 2015 Category: Allergy & Immunology Authors: Kataoka, T. R., Kumanogoh, A., Fukuishi, N., Ueshima, C., Hirata, M., Moriyoshi, K., Tsuruyama, T., Haga, H. Tags: Original Research Source Type: research

Mucolipin 1 positively regulates TLR7 responses in dendritic cells by facilitating RNA transportation to lysosomes
Toll-like receptor 7 (TLR7) and TLR9 sense microbial single-stranded RNA (ssRNA) and ssDNA in endolysosomes. Nucleic acid (NA)-sensing in endolysosomes is thought to be important for avoiding TLR7/9 responses to self-derived NAs. Aberrant self-derived NA transportation to endolysosomes predisposes to autoimmune diseases. To restrict NA-sensing in endolysosomes, TLR7/9 trafficking is tightly controlled by a multiple transmembrane protein Unc93B1. In contrast to TLR7/9 trafficking, little is known about a mechanism underlying NA transportation. We here show that Mucolipin 1 (Mcoln1), a member of the transient receptor potent...
Source: International Immunology - January 22, 2015 Category: Allergy & Immunology Authors: Li, X., Saitoh, S.-i., Shibata, T., Tanimura, N., Fukui, R., Miyake, K. Tags: Original Research Source Type: research

In vivo anti-LAP mAb enhances IL-17/IFN-{gamma} responses and abrogates anti-CD3-induced oral tolerance
Regulatory T cells (Tregs) play a critical role in the maintenance of immunological tolerance. The best-characterized Tregs are those expressing the transcription factor Foxp3 and in vivo modulation of Foxp3 Tregs has been employed to study their role in immune homeostasis. Latency-associated peptide (LAP) is a membrane-bound TGF-β complex that has also been shown to play a role in Treg function and oral tolerance. We developed a novel anti-mouse LAP mAb that allowed us to investigate the effect of targeting LAP in vivo on immune function and on anti-CD3-induced oral tolerance. We found that in vivo anti-LAP mAb admin...
Source: International Immunology - January 22, 2015 Category: Allergy & Immunology Authors: da Cunha, A. P., Wu, H. Y., Rezende, R. M., Vandeventer, T., Weiner, H. L. Tags: featured content Source Type: research

Dendritic cells in humans--from fetus to adult
The human immune system evolves continuously during development from the embryo into the adult, reflecting the ever-changing environment and demands of our body. This ability of our immune system to sense external cues and adapt as we develop is just as important in the early tolerogenic environment of the fetus, as it is in the constantly pathogen-challenged adult. Dendritic cells (DCs), the professional antigen-sensing and antigen-presenting components of the immune system, play a crucial role in this process where they act as sentinels, both initiating and regulating immune responses. Here, we provide an overview of the...
Source: International Immunology - January 22, 2015 Category: Allergy & Immunology Authors: McGovern, N., Chan, J. K. Y., Ginhoux, F. Tags: Invited review Source Type: research