ImmunoTox LetterJune2023

The 30th Annual Meeting of the JapaneseSociety of Immunotoxicology (JSIT2023)
1. DateSeptember 11-13th, 2023
2. Venues
Venue S: Shimadzu Tokyo Innovation Plaza

https://www.shimadzu.co.jp/aboutus/compan
y/access/tonomachi.html
Venue L: Life Science & Environment

research center (LiSE)
https://kawasaki-lise.jp/access.php
Venue R: TREX Kawasaki River Cafe

https://www.trex.style/
3. President

Ryosuke Nakamura, Ph.D.
(Division of Medicinal Safety Science,National Institute of Health Sciences,
Kawasaki, Kanagawa, Japan)
4. Main theme of the meetingNew immunotoxicity study required bysociety.
5. Meeting secretariat

Division of Medicinal Safety Science,
National Institute of Health Sciences.
E-mail: jsit2023@nihs.go.jp
URL: http://www.jsit2023.jp
6. Program (tentative)
30th Anniversary lecture

Immunotoxicology: Honor the Past andBuild the Future1) “The dawn of immunotoxicology – Immune
system as target organ of toxicity andimmuno-modulation by environmental
factors –”Takahiko Yoshida (4th Executive President)
2) “Significance of ICH S8 guideline andemerging issues thereafter”
Kazuichi Nakamura (5th ExecutivePresident)
Special lecture1) “Vaccine R & D in Japan: SCARDA

initiative”
Junichi Koga (Provost, Strategic Center ofBiomedical Advanced Vaccine Research andDevelopment for Preparedness andResponse, Japan Agency for Medical
Research and Development)2) “Immunotoxicity Assessment Using Bone
Marrow-Liver-Thymus (BLT) Immune
Humanized Mice (TBD)”
Kristina E. Howard, DVM, PhD. (ResearchVeterinary Medical Officer, US Food andDrug Administration)
Symposium: Immunotoxicity in the R&D of
New Modality Drugs and Vaccines

1) “Introduction”
kiko Ishii (Division of Biological Chemistryand Biologicals, National Institute ofHealth Sciences)
2) “Challenges in immunotoxicity evaluation
for AAV vector products”
Shogo Matsumura (Non-Clinical
Biomedical Science, Applied Research &Operations, Astellas Pharma Inc.)
3) “Non-clinical evaluation of CAR-T celltherapy, from the view ofimmunotoxicology”
Yukari Fujiwara (Preclinical Safety /Translational Medicine, Novartis Pharma
K.K.)

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ImmunoTox Letter4) “Immunotoxicity of oligonucleotide
therapeutics”
Yuko Nagayama (Global Drug Safety,
Biopharmaceutical Assessments Core
Function Unit, Eisai Product Creation
Systems, Eisai Co., Ltd.)
5) “Immunological studies for understanding
new modality of vaccines”
Yoshimasa Takahashi (Research Center for
Drug and Vaccine Development, National
Institute of Infectious Diseases)
6) Comprehensive discussion
Educational lecture“Cell death mechanism in severe drugeruptions”
Riichiro Abe (Professor, Division ofDermatology, Niigata University Graduate
School of Medical and Dental Sciences)
Special lecture of the recipient of the 13th
JSIT award“Establishment of a new concept “reproductiveimmunotoxicity” in immunotoxicology”
Kazuichi Nakamura (School of Veterinary
Medicine, Kitasato University (Organization
where the research was conducted))

Open symposium: Registration required, freeSpecial lectures of the recipients of the 13th
JSIT prize for encouragement“Immunological mechanisms of metal allergyand its prevention and treatment”
Toshinobu Kuroishi (Division of Oral
Immunology, Tohoku University Graduate
School of Dentistry)
Workshop: Animal Models and theAlternatives Reflect Human Immune

Responses: Current Status and Future
Prospects1) “Current status and prospect of drug
toxicity assessment using HLA transgenic
mice”
Shigeki Aoki (Laboratory ofBiopharmaceutics, Faculty ofPharmaceutical Sciences & Graduate
School of Pharmaceutical Sciences, ChibaUniversity)2) “Immunogenicity and toxicity evaluation
system of vaccine adjuvant using genomics
technology and humanized mouse model”
Eita Sasaki (Research Center for Drug andVaccine Development, National Institute ofInfectious Diseases)
3) “Review: Trial to construct the human type
immune tissues/organs and their possible
application”
Takeshi Watanabe (Institute for Life andMedical Sciences, Kyoto University)4) “Immunological characteristics related toage-associated pathogenesis in senescenceaccelerated mouse (SAM): Significance as amodel for evaluating immunotoxicity inelderly people”
Yasumitsu Nishimura (Department ofHygiene, Kawasaki Medical School)5) Comprehensive discussion

admission: Immunotoxicity Risk Assessment
for Chemicals in the Environment
1) “Health risk assessment of chemicalsubstances contaminated in theenvironment”
Yasunobu Aoki (Research Center for
Environmental Risk, Health Risk
Assessment Section, National Institute forEnvironmental Studies)2) “Risk assessment of quasi-drugs andchemical substances in food”
Reiko Teshima (Faculty of Veterinary
Medicine, Okayama University of Science)

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3) “Chemical exposures and allergic diseases
from epidemiological studies”
Kiwako Yamamoto (Allergy Center, andMedical Support Center of Japan
Environment and Children’s Study,
National Center for Child Health andDevelopment)
4) “Health hazards and risk assessment ofchemicals based on immunotoxicity”
Eiko Koike (Health and Environmental Risk
Division, National Institute forEnvironmental Studies)5) Comprehensive discussion
Oral sessions of young scientist
Oral presentations
Poster presentations
Luncheon seminars
7. Social gathering

TREX Kawasaki River Cafe
September 11, 18:00-20:00 (tentative)
https://www.trex.style/No.1（31）31

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The 12th Japanese Society of Immunotoxicology Award(The 2022 JSIT Award)
Immunological disturbance in arsenic-induced health effects

Seiichiro Himeno
Showa University, School of Pharmacy
Arsenic is an environmental pollutant that contaminates groundwater in many countries.
Exposure to arsenic causes skin disorders and cancers. Extensive studies havedemonstrated that exposure to arsenic also causes elevated mortality of cardiovasculardiseases and increased incidence of hypertension and diabetes. Since 2009, I have beencollaborating with Dr. Hossain of Rajshahi University, Bangladesh, to examine thehealth effects of arsenic among the residents in Bangladesh, focusing on common
diseases such as hypertension, atherosclerosis, and diabetes. We also investigated theeffects of arsenic exposure on asthma and its relation to immunological responses.
Determination of respiratory functions such as FEV1 and FEV6 using a Hi-Checker, acompact device that can measure respiratory functions, revealed that about 100 villagers
among over 800 study participants showed airway obstruction, with 70% of themshowing reversible airway obstruction (RAO). RAO is a feature suggestive of asthma
rather than COPD. The frequency of RAO increased dose-dependently with increasing
arsenic exposure markers, such as water, hair, and nail arsenic concentrations. The
frequency of the four major asthma symptoms, such as cough, wheezing, chest tightness,and shortness of breath, also increased by arsenic exposure dose-dependently. Since theRAO patients showed two times higher levels of serum IgE than non-symptom residents,
it is suggested that arsenic exposure enhanced the risk of allergic asthma. To test theinvolvement of immunological disturbance in developing asthma, we determined serumlevels of Th1/Th2 cytokines. Serum levels of IL-4, IL-5, and IL-13 were significantly
higher among arsenic-exposed residents, whereas those of IFN-ɤ or TNF-α were notelevated, suggesting the Th2 dominant shift of cytokines. Serum levels of eotaxin andperiostin were also enhanced by arsenic exposure, with significant correlations with Th2cytokine levels. We also found arsenic-induced elevation of IL-33, which is involved ininnate immune responses. Periostin is a clinical marker for asthma but is also involvedin other allergic symptoms such as atopic dermatitis. We found that serum levels of
periostin were higher among the residents with advanced-stage skin lesions than thoseNo.1（32）32

ImmunoTox Letterwith initial-stage skin lesions caused by arsenic exposure. Thus, the immunologicaldisturbance is important in various symptoms of arsenic-induced diseases, such asasthma and skin lesions. In addition, disturbances in tumor immunity may be involved
in arsenic-induced carcinogenesis in multiple organs, and decreased infection immunity
by arsenic exposure may lead to enhanced incidences of infectious diseases in children.
Further research on the mechanism of arsenic-induced dysregulation of immune
responses is required in the field of immunotoxicology.

Hossain Laboratory, Rajshahi University, Bangladesh

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The 12th Japanese Society of Immunotoxicology Prize for Encouragement
Study on immunotoxicity through mRNA stability control
mechanism

Ryuta Muromoto
Department of Immunology,
Faculty of Pharmaceutical Sciences,
Hokkaido University
I am deeply honored to have received the JSIT Prize for Encouragement for the year
2022. I would like to express my sincere gratitude to the selection committee, Dr.
Hiroyuki Kojima of Health Sciences University of Hokkaido, who recommended me forthe award, as well as my mentors and advisors. My research has focused on the analysisof regulatory mechanisms of cytokine signaling, particularly the function and regulationof Tyk2, a JAK family kinase, and STAT3, a transcription factor. Tyk2 deficiency impairs
signaling pathways involved in IL-23 and IL-17 production, leading to attenuated T cellmediated inflammation. Tyk2 has emerged as an important therapeutic target for
immune diseases, including psoriasis, and selective Tyk2 inhibitors have been developed.
My awarded project, "Study on immunotoxicity through mRNA stability control
mechanism," is related to the IL-17 response. I have studied IL-17 signaling in
keratinocytes, which play a role in psoriasis. Through microarray analysis, I identified I
κBζ as a protein specifically induced by IL-17. IκBζ was found to be involved in the IL17 response and the pathogenesis of psoriasis. I also investigated the mechanism of rapidIκBζ induction and discovered the mRNA stabilizing activity of IL-17, which is distinct
from other cytokines. Inhibition of this activity could potentially suppress IL-17-induced
inflammation. Dimethyl fumarate, an approved compound for multiple sclerosis
treatment, was found to inhibit IL-17 signaling by suppressing Regnase-1
phosphorylation. This suggests a partial explanation for its pharmacological effects.
Furthermore, I have explored the effects of environmental chemicals on the IL-17
signaling pathway, considering their role in chemical-induced immunotoxicity.
I am grateful to the JSIT for recognizing my research with the Encouragement Award.
This inspires me to further investigate cytokine signaling and its interactions with theNo.1（34）34

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environment, aiming to contribute to the prevention and treatment of immune-relateddiseases. I will continue my research in immunotoxicology and greatly appreciate theguidance and encouragement from the society.

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Immunotoxicological Research
Development of detection method in chemicalinduced respiratory allergy and the effect of allergic
response exposed estrogenic compound

Risako Tajiki
Laboratory of Short-term Toxicology,Toxicology Division
The Institute of Environmental Toxicology (IET)
As we known, the patients of occupational asthma have been increased in the world. But,
there is no generalized detectable method for chemical induced respiratory allergic
disease. Therefore, we would like to propose the experimental protocols of respiratory
allergic mouse model which detect some chemical having potential to respiratory
sensitizer. First, we selected two strains of mice such as BALB/c mice and NC/Nga micefor suitable strain for the respiratory allergic model in the preliminary study. We validated
the detection method of Trimellitic Anhydride (TMA)-induced respiratory allergy
combined dermal sensitization and inhalation challenge. Several allergic responses (IgE
level in serum, inflammatory cells and cytokine/chemokine levels in BALF) weresignificantly increased in TMA exposure groups. While, mice exposed negative control
talc were not increased cytokine/chemokine levels. When comparing strain difference
between BALB/c mice and NC/Nga mice, severe symptom in respiratory endpoints, thehigher amount of mast cells population in BALF and increased histamine level in serum
were only exhibited in NC/Nga mice. This experimental protocol and these differences ofNC/Nga mice and BALB/c mice was considered to be useful to detect the respiratory
allergic compound.
Recently, it is suggested that environmental chemicals aggravate several allergic
responses in some epidemiologic study. In this view point, whether bisphenol A (BPA),
chemicals having estrogenic potential, involved in the exacerbation of allergic
inflammation in second study. Then, we have conducted the allergic dermatitis and/or
allergic airway inflammation model using tolylene diisocyanate (TDI) to detect the BPA
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ImmunoTox Letteron immune disrupting effects by oral exposure before the challenge of TDI. In the allergic
dermatitis model, the thickness of challenge site (ear), cytokine levels were decreased inBPA exposure group. Conversely, eosinophil and cytokine levels in lung weresignificantly increased in BPA exposure group. These results suggest that BPA directly
affects allergies, but that the effects differ depending on the target organ.

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