ImmunoTox Letter
Educational lecture：June,2019

Yoshiya Tanaka (University of Occupational andEnvironmental Health, Japan)“Light and shadow of immunosuppressive drugs”

The 26th Annual Meeting of the Japanese

Kazuhiro Yatera (University of Occupational andSociety of Immunotoxicology (JSIT2019)

Environmental Health, Japan)“Environmental factor and pulmonary diseases”

1. DateSeptember 9-10th, 2019

Symposium: Inflammation and pathogenesis fromview point of immunotoxicology

2. Venue

Yasuhiro Yoshida (University of Occupational andKitakyushu International Convention Center,〒 802-0001

3-9-30, Asano, Kokura-Kitaku,

Kitakyushu, Fukuoka

Environmental Health, Japan)
Yasuo Morimoto (University of Occupational andEnvironmental Health, Japan)

3. President

Yasumitsu

Minoru Satoh, MD, PhD

University)(Professor,DepartmentofClinicalNursing,

University of Occupational and Environmental

Nishimura(Kawasaki

MedicalMaiko Hajime (University of Occupational andEnvironmental Health, Japan)

Health, Japan)
Workshop
4. Main theme of the meeting

Organizer: Shigeru Hisada (Aska Pharmaceutical)

Immunotoxicology“Development of immunotoxicology AOP and its- from basic science toclinical medicinegoal”
Hajime Kojima (National Institute of Health

5. Meeting Secretariat
Department of Clinical Nursing, University ofOccupational and Environmental Health, JapanSciences)
Shigeru Hisada (Asuka Pharmaceutical Co.)
Takumi Oishi (Bozo Research Center)

Tomoko Hasegawa (Secretary General)

Shogo Matsumura (Asteras Pharmaceutical Co.)

E-mail: jsit26-office@mbox.health.uoeh-u.ac.jp

Setsuya Aiba (Tohoku University)

URL: https://www.orbit-cs.net/jsit2019/index.html

Takao Ashikaga (National Institute of HealthSciences)

6. Program (tentative)
Sept 9-10
Special seminar：” Immunotoxicology of inhaled

Oral session

nanoparticles and the implications for lung diseasePoster presentation and discussion

susceptibility”

Luncheon Seminar

James C. Bonner, Ph.D.
Professor, Toxicology Program, Department ofSocial gathering

Biological

September 10, 18:30-20:30

UniversitySciences,NorthCarolina

State

JR Kyushu Kokura HotelNo.1（15） 15

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The 8th Japanese Society of Immunotoxicology Award(The 2018 JSIT Award)

Immunotoxicological evaluation of food allergens
Reiko Teshima
Faculty of Veterinary Medicine, Okayama University of Science
We have been studying the properties of substances involved in particular food allergenic
reactions and have conducted risk assessments. We have been focusing on the following twopoints: (1) the development of an evaluation method, and (2) the analysis of changes inallergenicity accompanying physical treatments of food allergens.
Regarding the first point, we constructed an in vitro digestion system using pepsin (SCG) or
pancreatin (SIF) to predict the allergenicity of food proteins. Furthermore, we constructed anallergen database (ADFS) to enable searches for sequence homology and to predict
cross-reactivity between novel proteins and known allergens.
Regarding the second point, we specifically searched for allergic reactions caused byhydrolyzed wheat protein (HWP), which was used as a quasi-drug, using both in vivo and invitro methods. HWP (Glupearl 19S (GP19S)), which is used in facial soaps, was produced by
the acid treatment of gluten (pH0.5-pH1.2) at 95℃ for 40 min. Reportedly, gluten treated with
0.1-N hydrochloric acid for 30 min at 100℃ exhibits a markedly increased IgE-binding capacitywith patient sera, suggesting the generation of neoepitopes on the gluten after treatment.
High-temperature acid treatments for a short time period resulted in the random degradation ofgluten, producing mixed short and long peptides and leading to a smear pattern when examinedusing electrophoresis. Furthermore, glutamine deamidated (Q → E) peptides were produced
during the treatment of gluten with acid and heat; this reaction may be responsible for theincrease in sensitization. The appearance of a deamidated-epitope (QPEEPFPE) after the acidhydrolyzation of wheat gluten was examined using an epitope-specific monoclonal antibody(mAb INRA-DG1). The appearance of the epitope was observed after 30 min of heating underacidic conditions (pH of about 1). Western blotting using this mAb seems to be useful for
identifying the existence of HWP-specific and highly sensitive epitopes.
As outlined above, we have been conducting research on immunotoxicological evaluations offood allergens from both basic and applied aspects.

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ImmunoTox Letter

The 7th Japanese Society ofImmunotoxicology Prize for Encouragement

Promotion of Developmental ImmunoToxicology (DIT) assessment
and Adverse Outcome Pathway (AOP)
Kiyoshi Kushima
Drug safety research labs., Astellas Pharma
It is my great pleasure and honor to be awarded the JSIT prize for encouragement. I would
like to express my sincere thanks to all of the members of the awarding committee.
My research history on an immunotoxicology started when I was graduate school student.
The experience I had during the student taught me the depth and fun of immunotoxicology
research. After graduation, I joined pharmaceutical company, where my research activity on adevelopmental immunotoxicology (DIT) initiated. Immune systems in pups, that is immaturecompare to that in adults, show different profiles in the effects on the chemical exposure. We
have reported the effects on the development of immunity in rat pups delivered from the dams
exposed by non-steroidal anti-inflammatory drugs (NSAIDs) during the gestation period.
Indomethacin, acetyl salicylic acid, or diclofenac sodium salt was administered once daily topregnant rats on days 18-21 of gestation. Indomethacin decreased the serum anti-KLH IgG
antibody titer in 3-week old male rats, while the serum levels of anti-KLH IgM, total IgM, andIgG unchanged. These changes disappeared in 8-week-old pups. Incubation of spleen cells
isolated from the 3-week-old pups with mitogen resulted in a suppression of Th2 cytokines,
suggesting that a change in the release of Th2 cytokines might involve the suppression ofantibody production. These results will contribute to the development of a technique for theassessment of developmental immunotoxicity.
We are now contributing the development of Adverse Outcome Pathway (AOP), that is a
new program lead by OECD. JSIT testing methodology committee established AOP working
group in 2015, in which we submitted a AOP regarding the suppression of T-cell dependent
antibody response by the calcineurin inhibitor. The AOP successfully passed an internal review,and external review is expected to start soon.
In the end, I would like to express my deepest appreciation to all of the people who involved,
supported and advised me for my research.

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ImmunoTox Letter

Immunotoxicological Research

Chronic arsenite exposure induces cellular senescencein mouse B lymphoma cell line A20 cells
Kazuyuki Okamura
National Institute for Environmental Studies
Epidemiologicalstudies

havereportedthatchronicarsenite

immunosuppression, however, the mechanisms are still controversial.

exposure

induces

Our previous study

suggested that arsenite exposure induced suppression of lymphocytes proliferation, leading toimmunosuppression, in vivo. The gene expression changes observed by arsenite exposure in vivo
were well reflected in mouse B lymphoma cell line A20 cells in vitro.

Thus, we further

investigated the mechanisms of arsenite induced suppression of cell proliferation in A20 cells.
After 24 hours arsenite exposure, we clarified that cell proliferation was inhibited via
cyclin-dependent kinase inhibitor p16 induction followed by p130 increase and G0/G1 arrest. We
further showed that long-term arsenite exposure until 14 days induced morphological changes of thecells, which was not observed in 24 hours exposure. In addition, strong induction of G0/G1 arrest
via p130, appearance of senescence-associated β-galactosidase positive cells and irreversible growth
suppression were observed in the cells after long-term arsenite exposure.
consistent with cellular senescence.

These features areWe also found that the expression of activation-induced

cytidine deaminase (Aid) was prominently up-regulated, and several DNA repair-related enzymes
were down-regulated after long-term arsenite exposure. These results suggested that long-term
arsenite exposure induces cellular senescence via DNA damage accumulation in lymphocytes.

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