ImmunoTox Letter
The 24th Annual Meeting of the JapaneseJune,
2017

Society of Immunotoxicology
Date

The 6th Japanese Society ofImmunotoxicology Prize for Encouragement

September 4th - 5th, 2017 (Meeting)
September 3rd, 2017 (Lecture open to local citizens)

Effects of environmental chemicals onVenue

immune response via nuclear receptors

Lecture room at School of Veterinary Medicine, Kitasato

Hiroyuki Kojima
Department of Environmental and Health Sciences,
Hokkaido Institute of Public Health

University35-1 Higashi-23-bancho, Towada, Aomori 034-8628, JapanPresident
Kazuichi Nakamura (Kitasato University)

It is my great pleasure and honor to be awarded theJSIT prize for encouragement. I would like to sincerely
thank all of the members of the awarding committee.

Main theme of the meeting
New

Nuclear receptors, including several hormone receptors,

perspectiveof“immunoenhancement”

and“immunosuppression”

form a ligand-dependent transcription factor that regulates
the genes involves in key physiological functions, such as

Aim of the meetingcell growth and differentiation, development, homeostasis,

Autoimmunity or allergy is not necessarily initiated byand metabolism. Between 1998 and 1999, I studied the“immunoenhancement”, but can be caused by evenmechanisms underlying nuclear receptor-induced gene

immunosuppression or normal immunity recognizing

expression as a visiting researcher at the National Institutealtered-selfof Environmental Health Sciences (NIEHS/NIH, USA).

immunosuppression during pregnancy may be impaired by

After coming back to Hokkaido, Japan, I had shown thatxenobiotics.

environmental chemicals, such as plasticizers, pesticides,“immunosuppression” as the phenotype of immunotoxicity

and dioxins, can function as ligands of nuclear receptors.

need to be redefined.

In particular, our findings using cell-based transactivation

be discussed from new perspectives.

antigenorMHC.

Physiological“Immunoenhancement”

andIn this meeting, immunotoxicity will

assays revealed that a number of environmental chemicals
show estrogen receptor (ER)α, ERβ and pregnane X

azole-type fungicides and isoflavones, such as biochanin A

receptor agonistic activity as well as androgen receptor

and genistein, can act as modulators of interleukin-17 geneantagonistic activity. These experiences provided me withexpression via nuclear receptors, RORα and RORγ, in

my present research theme “the immunotoxicologicalimmune cells (Kojima et al., 2012; 2015; Takahashi et al.,effects of environmental chemicals via nuclear receptors”.

2017). In the future, I want to clarify the effects of chemical

However, although some nuclear receptors have beenreported to have important roles in the immune systems,
theimmunotoxicologicaleffectsofenvironmental

mixtures on cytokine production via nuclear receptors.
Finally, I would like to give an appreciation to Dr. Ryuta
Muromotoat

Hokkaido

chemicals via nuclear receptors have not been fully
collaborators for their help.
understood. To date, we provided evidences that several
azole-type
No.1（7） 7University,andallmyImmunoTox Letter
Koumei Shirasuna1, Nao Tanikawa1, Ayae Ozeki1,

Organizing Committee

4.

Tetsuo Aida (Daiichi Sankyo Co., Ltd.)

AkihideEtsushi Kuroda (Osaka University)

University of Agriculture, 2Jichi Medical University)

Ohkuchi2,

Masafumi

Takahashi2(1TokyoHayato Terayama (Tokai University)“Mechanisms of pregnancy complications caused byYasuo Yoshioka (Osaka University)

nanoparticles: possible role of sterile inflammation(inflammasomes) during pregnancy”

Lecture open to local citizens
WorkshopFujio Kayama (Jichi Medical University)“Safety of rice as a staple food: Findings derived fromnationwide epidemiological study in cadmium intake”“The latest developments in the safety evaluation methodof biopharmaceuticals (protein formulations)”
1.

Akiko Ishii-Watabe (National Institute of HealthSciences)

Special lectures“Outline and Points to Note on the Safety Evaluation

1.

Method of Biopharmaceuticals”

Danuta Herzyk (Merck Research Laboratories)“Immunotoxicity assessment of biopharmaceuticals”

2.

2.

Kazushige Maki (Pharmaceuticals and Medical

Tsuyoshi Yokoi (Nagoya University Graduate SchoolDevices Agency)of Medicine)“Consideration for preclinical Safety Evaluation of“Involvementofimmune-related

factors

Biotechnology-Derived Pharmaceuticals”

onidiosyncratic drug-induced liver injury”

3.

Chiyomi Kubo (Chugai Pharmaceutical Co., Ltd.)“Characteristic test methods in biopharmaceutical
nonclinical evaluation

Educational lecture- Evaluation methods using human cells –”Takeharu Minamitani (National Institutes of Biomedical
4.

Innovation, Health and Nutrition)“Nonclinical safety assessment of antibody-drug“Autoimmune diseases induced by virus infection”

conjugates”

Symposium“Reproductiveimmunotoxicology:

ImmunologicalLuncheon seminar
Day 1: Vanessa Peachee (Charles River Laboratories

mechanism of pregnancy and its breakdown”
1.

Ashland)

Yosuke Maeda (Kitasato University)“Unraveling immunotoxicological assays for“Immunological changes during pregnancy in cows”
2.

3.

YoshieKametani(TokaiUniversity

Tetsuo Aida (Daiichi Sankyo Co., Ltd.)

Schoolof

pharmaceutical and agrochemical industries”
Day 2: Asako UchiyamaMedicine)(Shin Nippon Biomedical Laboratories, Ltd.)“Immune tolerance in placenta”“Evaluation methods for cell and gene therapy
products in SNBL”

Tomoko Shima, Akitoshi Nakashima, Shigeru Saito(University of Toyama)“Regulatory T cells are important for implantationand maintainance of pregnancy”

Meeting Secretariat
Laboratory of Toxicology, School of Veterinary Medicine,Kitasato University
Ryo Kamata (Secretary General)
E-mail: secretariat@jsit2017.jp

No.1（8） 8

ImmunoTox Letter

Real Voices of International
Immunotoxicologists

Immunotoxicological Research
Analysis of the mechanism involved in

What the other researchers think about? How can I do

the effect of environmental factors on livingorganisms through immunological researchmore exciting research in the future? Most of the young
Japanese immunotoxicologists may hope to listen to some

Naoko Kumagai-Takei

kind of comments from the experts in this field, in(Department of Hygiene, Kawasaki Medical School)

particular from the outside of Japan. This time, weinterviewed Dr. Victor J. Johnson from Burleson Research

I am studying the effects of asbestos exposure on thedifferentiation and function of cytotoxic T lymphocytes

Technologies, Inc., USA. Let’s go to listen to his voice.
What will you feel and learn?

(CTLs) at the Department of Hygiene, Kawasaki MedicalSchool. I have reported that exposure to chrysotile B

Victor J. Johnson, Ph.D.

asbestos suppressed the induction of human CTLs during
mixed lymphocyte reactions, and was accompanied bydecreased levels of IFN-γ and TNF-α, and the proliferationof immature CTLs (Am J Respir Cell Mol Biol 49: 28-36,
2013). Recently, I also reported that IL-2 insufficiency was
not the main cause for the suppressed induction of CTLs
by asbestos exposure, although the potential for animprovement of such suppressed CTL functions wassuggested(JImmunolRes

2016:7484872,2016).

Additionally, I found that patients with malignant
mesothelioma showed decreased perforin levels in CD8+lymphocytes following stimulation compared to patientswith pleural plaque and healthy volunteers (J Immuno Res
2014: 670140, 2014).
In future, I would like to analyze the mechanisms
involved in the immunological effects of environmental
factors on living organisms at the organ, cellular andmolecular levels. In particular, I wish to elucidate themechanism of asbestos-caused suppression of the immune
response in CTLs, as well as identifying molecules that canassist in the improvement of asbestos-caused suppressed
CTL functions.

No.1（9） 9

Director of Operations
Principal Investigator for Immunotoxicology for theNational Toxicology Program
Burleson Research Technologies, Inc.
Morrisville, North Carolina, USA

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

and great beer and sake too. As you can see from mylong-winded response, and I could go on, I enjoyed every
aspect of my journey in Japan, memories for a lifetime.

My trip to Japan was amazing and it is very difficult for

Thanks so much!

me to identify the single most impressive event orexperience. I enjoyed every aspect of my journey in Japan.

Q2. What is the most exciting thing in your career to date?

If I had to narrow it down, I would need to share two
experiences to be fair to my trip. First, I was very

I have been studying Immunotoxicology for the past 20

impressedtheyears have had many exciting moments in my career

immunotoxicologists in Japan and the breadth of theranging from research findings, networking with respected

research that they are exploring. The majority of theimmunotoxicologists,

meeting was in Japanese, however, I felt that I was able toimmunotoxicology to budding young immunotoxicologists.

understand and keep up to the presentations; a testament

I started my career in immunotoxicology reading the works

to the quality of the science. My lecture was given inof Dr. Michael Luster and was fortunate enough to meet

English and was well received by the audience, making mehim

feel accepted among the Japanese Immunotoxicology

Immunotoxicology. Eventually, I was blessed to be able tocommunity. Equally impressive as the science was myjoin

experiences of the people, culture, and places of Japan. The

Occupational Safety and Health, where we worked on

hospitality provided to me was paralleled by none other. I

mechanisms and susceptibility to occupational asthma andwas given the privilege of a grand tour of Japan and I owe

rhinitis. Many years of hard work lead to being recruiteda special thanks to many people including Dr. Yasuoto my current position at Burleson Research Technologies

Morimoto, and his team of organizers for the meeting, I(BRT), an immunotoxicology CRO, and the opportunity tomet many great scientists. I was treated to the great foodcompete for a premiere contract in the field. The mostculture of Japan with many members of JSIT. I would like

exciting development in my career to date was being

to send a big thanks to Alice Kayama for hosting me on aawarded the Immunotoxicology Contract for the National

tour of the highlights of Fukuoka Prefecture including myToxicology Program, NIEHS, NIH, and cherish all the hardfirst visit to a Japanese Castle, Kokura Castle. I also

work and perseverance that was required to get to thisexpress sincere gratitude to my longtime friend andpoint. Achieve your goals, it is very rewarding.

bythetalent

andenthusiasm

ofcolleague, Dr. Masashi Tsunoda. Masashi and I set off on
an ambitious tour of Japan, including people, culture, andarchitecture. Our journey started in Kokura, travel by rail(including my first ride on a bullet train!) and foot (somedays reached over 40,000 steps!!!) to many great cities tosee famous castles, temples, and heritage sites. Thanks forthe great fun! Masashi and I split ways in Tokyo where I
met another great friend and colleague, Dr. Fujio Kayama.
Fujio and I shared some great food and conversation, oh,and great beer and sake too. As you can see from myNo.1（10） 10

at

his

anannuallaboratory

toteaching

meetingat

theof

thescience

theNationalSociety

Instituteofoffor

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

Q4.

Whatisrequiredfor

breakthroughinimmunotoxicology research in the future, do you think?

My career focus in on immunotoxicology safety

Presenting your discoveries, responding to constructive

assessment and generation of quality data for humancriticism, networking, and keeping up with the cutting edge

health risk assessment. Working at BRT allows me to studyof immunology and toxicology are key to prospering in thethe effects of novel drugs on the immune system andfield of immunotoxicology. Immunotoxicology is an applied

contribute to safety evaluation for drug candidates prior todiscipline,

their entry into the public domain. Being the Principal

toxicology and applying them to protection of the immune

Investigator for Immunotoxicology for the Nationalsystem

Toxicology Program provides me the opportunity to

immunotoxicologists will come from hard work and theconduct

andwillingness to venture outside of your comfort zone. Meetoccupational chemicals of public concern. This type ofas many people as you can as they are the ones that can

research is critical to a comprehensive approach to humanstimulate your next great idea and provide you thehealth risk assessment and is my passion and the mission of

intellectual and financial support to work towards the next

our research programs at BRT.

breakthrough. Share ideas and critical thinking, it will help

similarresearchonenvironmental

istaking

ourconcepts

charge.

from

immunology

Breakthroughs

forandnew

make strides in your career. An area of research that isgaining popularity in toxicology and immunotoxicology isaddressing the role of the microbiome in our science. The
microbiome is the collection of microorganisms that live onand within us and are critical to health. Thesemicroorganisms are at all portals of entry to the body andcan participate in xenobiotic metabolism ultimately
influencing absorption and distribution of xenobiotics andtheir potential for immunotoxicity. Recent research
indicates that the microbiome influences development of
the immune system and can play a driving role or canmitigate immunotoxicity. Many breakthroughs are on thehorizon through incorporation of the microbiome into thefields of immunotoxicology and toxicology.

No.1（11） 11