ImmunoTox Letter
Diseases, Institute for Advanced Medical Sciences, HyogoDecember,2015

College of Medicine)

Report from the 22nd Annual Meeting of theSymposium

Japanese Society of Immunotoxicology“Toxic’ effect to ‘disrupting’ effect”(JSIT2015)

1.

Hirohisa Takano
Kyoto University

Aggravating effects of Asian sand dust and PM2.5 onlung inflammation and allergic inflammation(Takamichi Ichinose, Department of Health Sciences, Oita
University of Nursing and Health Sciences.)

The 22nd Annual Meeting of the Japanese Society ofImmunotoxicology (JSIT2015) was held at International

2.

Environmental

chemical-inducedinflammatory

Clock Tower Centennial Hall International Conference

response and disruption of immune cell function

Hall, Kyoto University, Kyoto during September 10-11,(Eiko Koike, Center for Environmental Health Sciences,

2015. The main theme of this meeting was “RevolutionaryNational Institute for Environmental Studies)

perspectives in the field of Immunotoxicology -Toxic effects
and Disrupting effects-”. The meeting consists of a special

3.

Impact of exposure to environmental chemicals onlecture, 2 educational lectures, one symposium andobesity and obesity-related metabolic disorders.

workshop, 2 luncheon seminars, JSIT Research Award(Rie Yanagisawa, Center for Environmental Health

Lectures, 11 oral presentations and 16 poster presentations

Sciences, Biological Impact Research Section)

including 3 student and young scientist presentations.
4.

Effects of prenatal and lactational exposure toSpecial lecture

low-dosesofThe influence of early immune signaling and thedevelopment

bisphenolA

onmurinebrain

microbiome on immunomodulatory responses following(Kyoko Itoh, Department of Pathology and Applied

exposure to the antimicrobial triclosan

Neurobiology, Graduate School of Medical Science, Kyoto(Stacey E. Anderson, NIOSH, Morgantown, WV)

Prefectural University of Medicine)

Master’s Lecture

5.

1.

environmental chemicals

Stress signaling and disease(Hidenori Ichijo, Laboratory of Cell Signaling, Graduate

Airborne

fineparticles

andallergic(TaisenIguchi,Okazaki

Institutefor

Integrative

Bioscience, National Institute for Basic Biology, National

School of Pharmaceutical Sciences, University of Tokyo)
2.

Reproductive and endocrine disruption induced byrhinitis:

Institutes of Natural Sciences)elucidation of allergic rhinitis exacerbation mechanism andthe development of therapeutic techniques using mousemodel of allergic rhinitis(Tomohiro Yoshimoto, Department of Immunology,
Hyogo College of Medicine. Laboratory of Allergic
No.2（13） 20

ImmunoTox Letter
Workshop: “Immunotoxicity testing Q and A”“JSIT prize for encouragement” were received by Dr.

0. Immunotoxicity testing Q and A.

Etsushi Kuroda, ( Laboratory of Vaccine Science, WPI(Shigeru Hisada, Research and Development Division,Immunology Frontier Research Center, Osaka University,

ASKA Pharmaceutical Co., Ltd.; Tadashi Kosaka, StudyOsaka),

Title:

The

underlying

mechanismsofManagement Division, The Institute of Environmental

particulate-induced immune responses and inflammations

Toxicology)-Particulate adjuvant and immunotoxicity-, and Dr. Rie
Yanagisawa (Center for Environmental Health Sciences,

1. Current status of flow cytometry measurement at

Biological Impact Research Section), Title: Impact ofenvironmental pollutants on lifestyle related diseases -fromclinical laboratories- To think about non-clinical measurement items -the point of view of immunotoxicology-.

(Atsushi Momobayashi, Molecular Genetic Analysis“The Best Presentation Award” was received by Dr. Eita
Sasaki (Department of Safety Research on Blood andDepartment, LSI Medience Corporation)

Biologicals products, Institute of Infectious Diseases). Title:
2. Immunologic tests and evaluation of the risk for

Establishment for a next generation safety evaluatingchemical-induced autoimmunity induced by chemicals inmethod for influenza vaccine and adjuvants usinghuman

humanized mouse model.

(Minoru Satoh, Department of Clinical Nursing, School“The Student and Young Scientists Award” was given toof Health Sciences, University of Occupational andMr. Takato Kusakabe (Laboratory of Adjuvant Innovation,

Environmental Health, Japan)

National Institute of Biomedical Innovation, Health andNutrition (NIBIOHN), Laboratory of Vaccine Science,

3. A case of evaluation of the immunotoxicity data having

Immunology Frontier Research Center (IFReC), OsakaUniversity).

wide variations such as the production of antibody(Takumi Ohishi, Gotemba Laboratory, BoZo Research

Title:

Application

ofhydroxypropyl-β-cyclodextrin, a small compound as apotent DAMPs inducer, for mucosal adjuvant.

Center Inc.)

4. Appropriate trial plan and analysis method for TDAR

I would like to appreciate all the participants who actively(Satoru Fukinbara, Data Science Expert Committee,

joined presentations and discussions.

Drug

Evaluation

Committee,

JPMA,

DataScience

Development Headquarters, Ono Pharmaceutical Co.,LTD.)In this year, “JSIT Research Award” was received by Dr.
Jun-ichi Sawada (Pharmaceuticals and Medical Devices
Agency). Title: Effects of genetic polymorphisms on
anti-cancer drug-induced myelotoxicity.

No.2（14） 21

ImmunoTox Letterare following: inactivated whole trivalent influenza vaccine

The Best Presentation Award(WPV);

Establishment for a next generation safety
evaluation method for influenza vaccine andHA

influenzavaccine.

Thevaccine

wasintraperitoneally injected to the mouse at a dose of 0.5mL/mouse. The day following the vaccination, the lung andblood were collected and analyzed leukocyte population,adjuvants using humanized mouse model

gene expression.

Eita Sasaki1, Takuo Mizukami1,Results and Discussion: Stable engraftment of human

Haruka Momose1, Kazunari Kamachi2, Hiroshi

PBMC in huPBL-mouse was observed after 2 weeks of

Yamada3, Ken J Ishi4,5, Isao Hamaguchi1

transplantation. Both human CD4 and CD8 positive cells
were also detected in the PB after 2 weeks transplantation.

1

Department of Safety Research on Blood and biologicals

Similar to T cell lineage, CD19+B cell could also be seen inproducts, Institute of Infectious Diseases

the PB after 2 weeks after transplantation. We could detect

Department of Bacteriology II, Institute of Infectious Diseases

more than 50% of human CD45 positive cells derived from23National Institutes of Biomedical Innovation, Health andNutrition. Toxicogenomics and Informatics Project

donor human PBMCs at 3 weeks after the transplantation.
These preliminary result suggest that vaccine treatment for

4National Institutes of Biomedical Innovation, Health andNutrition. Laboratory of Adjuvant Innovation

safety evaluation should be carried out at 3 weeks after theLaboratory of Vaccine Science, Immunology Frontier

PBMC transfer. In addition, the some biomarker genes

Research center, Osaka University

expression were increased in WPV vaccinated mice5

compared with SA-treated mouse.
Aim: Vaccination is a most beneficial and universal tool

Based on these results, the new vaccine safety test

to prevent infectious disease. To ensure the safety ofmethod using Hu-PBL-mouse might be useful for safety

vaccinations, the abnormal toxicity test (ATT, also known

assessment

as general safety test) have introduced to the vaccine rot

extrapolation for the marker genes were partiallyrelease testing. Recently, many types of influenza vaccines

indicated.

andadjuvants

weredevelopedtoenhanced

immunogenicity. To cover many types of influenza vaccine,
we tried to develop new safety test using gene expression
profiling. We successfully identified 20 biomarker genes toevaluate the safety of influenza vaccine. On the other hand,
extrapolation of the result from animal experiment tohuman is important for safety assessment. Therefore, inpresent study, we attempted to establish a next generation
safety testing method for vaccine and adjuvant using
humanized mouse model.
Materials and Methods: Human peripheral bloodmononuclear cells (PBMC)-engrafted NOG mice were used
as a huPBL-mouse model. The vaccines using this study
No.2（15） 22ofhumanand

thepossibilityoftheImmunoTox Letter
functioned as adjuvant and induced not only systemic but

The Student and Young
Scientists Award

also mucosal immune responses. In addition, HP-β-CD byi.n. administration induced a low antigen-specific IgEApplication of Hydroxypropyl-β-cyclodextrin,a small compound as a potent DAMPs inducer,responses. For the clinical use of HP-β-CD as mucosal
adjuvant,

intranasal

administrationof

HP-β-CD-adjuvanted influenza hemagglutinin split andfor mucosal adjuvant
Takato Kusakabe(Laboratory of Adjuvant Innovation, National Institute ofinactivated whole-virus influenza vaccine result in thesecretion of vaccine-specific antibody and protected mice

Biomedical Innovation, Health and Nutrition (NIBIOHN),

against a lethal challenge with influenza virus. TheseLaboratory of Vaccine Science, Immunology Frontier Research

results suggest that HP-β-CD may be a potent mucosal

Center (IFReC),Osaka, Japan)

adjuvant for seasonal and pandemic influenza vaccine.

My name is Takato Kusakabe working in National
Institute of Biomedical Innovation, Health and Nutrition(NIBIOHN). I am very happy and honored to be the best

Immunotoxicological Research

Young presenter Award at the 22th Annual Meeting of theJapanese Society of Immunotoxicology. I would like to

The effects of air pollutants on respiratory

appreciate the support from the selection committee andand immune systemgive special thanks to my research professor Dr. Ken Ishii,Akiko Honda

Dr. Etsushi Kuroda and other colleagues in my laboratory(Kyoto University)

for supporting throughout the progress.
In

thisstudy,

wetriedtoapply

The aim of my study is 1) to elucidate the effects of air(HP-β-CD)

formucosal

pollutants such as Asian sand dust particles (ASD) andadjuvant. Mucosal vaccine is an attractive and valid

particulate matter with aerodynamic diameter ≤ 2.5 µm

alternative to current vaccines because it has a potential to(PM2.5) on respiratory diseases, especially asthma, 2) toinduce local immune responses at the site of entry of theclarify the mechanism by which air pollutants cause

pathogens. However intranasal routes are generally lessdevelopment/exacerbation of asthma, 3) to identify theimmunogenic and frequently induce tolerance. To resolve

responsible components and factors of air pollutants

these problems, safe and effective adjuvants for mucosal

contributing to asthma. We provided evidence that ASD

vaccines are required. Recently, we reported that HP-β-CD

reduced cellular viability and facilitated pro-inflammatory

has the adjuvant activity and induces antibody responses.

responses in airway epithelial cells, and that ASD alsoThis adjuvant effect is similar to Alum, which is the mostactivated the network of antigen presenting cells (APC)

widely used adjuvant in human. Because Alum is particle

andadjuvant, it is difficult to use for mucosal administration.

Furthermore, we indicated that the difference in the events

Accordingly, taking advantage that HP-β-CD is soluble toof ASD and in heat-sensitive components adhered to ASD

water, we tried to apply HP-β-CD for mucosal adjuvant.

could enhance the health effects (J. Appl. Toxicol.,We found that intranasal (i.n.) administration of HP-β-CD

34:250-257, 2014). Subsequently, we examined the effects ofhydroxypropyl-β-cyclodexrin

No.2（16） 23

subsequent

immuneresponsevia

lymphocyte.

ImmunoTox Letterheat-sensitive components adhered to ASD such as

and toxic epidermal necrolysisa, since these adverse events

Bjerkandera adusta (B.ad) or Benzo[a]pyrene (BaP) on

are sometimes fetal for patients. In addition to the research

respiratory and immune system. The research results

activities, I am involved in making Adverse Outcome

indicated that B.ad rather than BaP contributed toPathway (AOP) of immunosuppressant to develop thedevelopment/exacerbation of asthma, especially to thealternative test assay of animal testing, as a member ofimmune system via APC.

AOP committee of JSIT. I will continue to make an effort

The final goal of our research is to contribute to theprevention and treatment strategy of the health effects

to work on drug allergy and immunotoxicolology with
helpful advice and support from JSIT members.

caused by air pollutants, and to suggestion of monitoring
components.

Words fromNew councilors
Words fromNew councilors

Greeting to becoming a new councilor

Greeting to becoming a new councilor

Chemicals Evaluation and Research Institute, Japan

Masahiro Takeyoshi

memberI would like to thank members of the Board of Directors

Kiyoshi Kushimaof the JSIT for accepting me to serve as a councilor. I

Drug Safety Research Labs., Drug Discovery
Research, Astellas Pharma Inc.

started my career at Chemicals Evaluation and ResearchInstitute (CERI) in Hita city, Oita Prefecture, engaging inI would like to take opportunity to express my sincere

Local Irritation, Sensitization and Antigenisity studies ofappreciation to the Board of Directors of the Japanesechemicals. Then I am currently managing the development

Society of Immunotoxicology for accepting me as awork for safety evaluation method for chemicals based oncouncilor. The approval gives me great pleasure.

omics technology, such as genomics, proteomics andI started research of immunology at Hiroshima--University, where the role of CD4 CD8 （double negative）Tmetabolomics, and assay methods for biological activities
for biologics in a laboratory at Saitama Prefecture.

cell and γδ-T cell in the hormone-stress-immune network

Guinea pig prediction test for skin sensitization of

was explored. After joining to Astellas Pharma Inc., I havechemicals employs skin reaction as an endpoint to decide

been engaged in an evaluation of adve rse effect,

positive/negative judgment, and it may makes ambiguous

especially immunotox icology /developme nta ljudgment. My research driving force in these days was toimmunotoxicology of developing drugs. Throughout myclarify the judgment of sensitization test results. So I haveresearch, effects on immune function of non-steroidal

tried to elucidate the antigen reactive lymphocyte byinflammatory drugs (NSAIDs) were indicated in rat pups

cytokine release after cloning the guinea pig interleukin-2

exposed through dams. Further, my recent interest is tocDNA. And I also introduced the technique of local lymph

c l ar i f y t h e me c ha ni s m o f dr ug - i n d uc e d s e v e renode assay from Dr. Ian Kimber, and then developed theallergy/hypersensitivity, i.e. Stevens-Johnson syndrome

non-RI alternative of this method that was endorsed asand toxic epidermal necrolysisa, since these adverse events

OECD TG442b.

No.2（17） 24

ImmunoTox Letter
I will try to make meaningful contributions to theQ2. What is the most exciting thing in your career to date.

Japanese Society of Immunotoxicology. I hope to inspire
your further guidance and encouragement.

After 11 years in the field of immunotoxicology, I would
have to say that the most exciting thing that has happen in
my career is watching how my team has evolved duringthat time.

Real Voices of International
Immunotoxicologists

technicians, student interns, and post-docs during thattime.

What

non-Japanesescientists

think

I have mentored and worked with numerous

about

immunotoxicology? What they have experienced and will
do future. Their comments would allow us to realize thesignificance of study about immunotoxicology. This time,
we interviewed Dr. Stacey Anderson from National

It is very rewarding to me to know that I havecontributed to their success.

My first doctoral student isplanning to graduate in May and has already accepted a
post-doctoral position in a very respected laboratory.

It isa wonderful feeling to know that I was part of her growthand development into an independent thinking scientist.

Institute for Occupational Safety and Heath, USA. Let’s go
to hear his voice. What do you feel and get from it?

Stacey Anderson, Ph.D.
National Institute for Occupational Safety and Heath
Team Leader, Hazard Identification and Immunotoxicolgy
Allergy and Clinical Immunology Branch
1095 Willowdale Dr. M/S 4020
Morgantown, WV 26505

Q1. What was the most impressive event for you in yourtrip to Japan this time?

I would like to start by saying that my first trip to Japanwas impressive in many ways. I found Kyoto to be a truly
unique place with tremendous amounts of beauty andculture.

In addition, the organizers and hosts of themeeting made my husband and I feel very welcomed.
Their descriptions of the local cuisine and customs weremuch appreciated.

I would also like to say that I was very

impressed by the large number of immunotoxicologists inJapan especially since it is considered a relatively new fieldof science.

Dr. Stacey Anderson

No.2（18） 25

ImmunoTox Letter
Q3. What are the things you are doing energetically, rightnow?

been identified to be important regulators of the adaptive
immune response.

However, there is very limited research

investigating how chemicals affect the innate immune
We have a lot going on in my laboratory right now!

Isystem and ultimately hypersensitivity or other abnormal

used my lecture as an opportunity to try and capture theimmune responses.

key areas of research that we are currently focused on andaspects of the immune system may help to guideexcited about.

immunotoxicological

We are really interested in understanding

how chemicals influence allergy and asthma.

A better understanding of theseresearchefforts.

ItisveryOne

important that we expand our way of thinking toimportant class of chemical that we have been interested inencompass novel mediators of allergic disease, such as theareinnate immune system, in our efforts to treat and prevent

antimicrobials

anddisinfectants.

While

this

classification covers a very large number of chemicals, we

chemical-induced immune disorders.

have identified several conserved and unique mechanisms
bywhichthiskindofhypersensitivity responses.

chemicalcaninfluence

We feel that this research

has identified several novel mediators of allergic diseasesuch as the innate immune system, additional T-cell
pathways, the microbiome, and regulatory RNA.

Q4.

Whatisrequiredforbreakthroughinimmunotoxicology research in the future, do you think?

Over the last decade there has been a remarkableincrease in the incidence of allergic disease and one
potential contributor is the increasing number of chemicalsin production with an estimated 700 new chemicals
introduced annually.

Before we can reduce the incidenceof this disease we must understand the responsible agentsand t he u nde r l y i ng me c hani s ms .

T he f i e l d ofimmunotoxicology is very dynamic especially with respect
to the immunology component.

It seems that something

new is discovered every week in the field of immunology
and that is why it is very important to stay on top of thecurrent trends in this field.

These new discoveries canp r o v i d e i mp o r t a n t n e w a r e a s o f r e s e a r c h f o r
immunotoxicologists which may help us to better
understand the effects of chemicals on the immune system.
Recently components of the innate immune system haveNo.2（19） 26