ImmunoTox LetterJune
2024

The 31th Annual Meeting of the JapaneseSociety of Immunotoxicology (JSIT2024)
1. DateSeptember 19-20th, 2024
2. Venues

2) “Development of AIDS prevention andtreatment vaccines using live attenuatedvaccines expressing adjuvant molecules.”Yasuhiro Yasutomi (National Institute of
Biomedical Innovation, Health andNutrition)3) <TBA>A Lecture by an invited speaker from
SOT/ITSS.

Heisei Kinen Kaikan, Hyogo Medical

Symposium１

University（The following link is for Hyogo Medical University

Environment and Allergy: Latest Findings

Nishinomiya Campus :https://www.hyomed.ac.jp/about/access/campus_map/nishinomiya/）

3. President

Etsushi Kuroda.
(Department of Immunology, School ofMedicine, Hyogo Medical University,Nishinomiya, Hyogo, Japan)
4. Main theme of the meeting

Scientific Exploration of Environment andHealthcare through ImmunotoxicologicalResearch.

Symposium 2
The Efficacy and Safety of New Vaccines andImmunotherapies
1) “CpG ODN-mediated immunoprophylaxis

5. Meeting secretariat

Department of Immunology, School ofMedicine, Hyogo Medical University.
E-mail : jsit2024@hyo-med.ac.jp
URL :https://www.japanimmunotox.org/jsit20
24/index.html
6. Program (tentative)
Special lecture1) “Development of methods for assessing
respiratory sensitizing potential.”
Takayuki Yoshimoto (Tokyo Medical

1) “Environmental factors that disrupt theepithelial barrier, leading to allergic
inflammation.”
Hideaki Morita (National Center for Child
Health and Development)2) “Molecular and cellular mechanisms
through which tissue-resident memory Tcells drive refractory disease formation.”
Kiyoshi Hirahara. (Chiba University)
3) “Exploration of prevention/exacerbation
factors for allergic rhinitis using mousemodels.”
Kazufumi Matsushita (Hyogo Medical
University)against viral infection”
Kouji Kobiyama (The University of Tokyo)
2) “Disease modifying treatments: Allergy
immunotherapy for type-1 allergy”
Katsuyo Doi (Torii Pharmaceutical Co Ltd)
3) “Preclinical immunogenicity and protective
efficacy of new mRNA vaccines against
Severe Fever with Thrombocytopenia
Syndrome, SFTS”
Shiori Egasira (Daiichi Sankyo Co Ltd)

University)No.1（24）24

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Special lecture of the recipient of the 14th
JSIT award“Immunotoxicology; the origins of medicine
that protects lives in interaction withenvironment.
－From segmented research to research withan integrated perspective－”
Takahiko Yoshida (Professor emeritus,Asahikawa Medical University)

1) “Strategy and case studies for assessing
immunogenicity of biopharmaceuticals.”Eri Hamamura (Daiichi Sankyo Co Ltd)
2) “Immunogenicity assessment anddeimmunization strategy of engineered
therapeutic antibodies.”
Eiichi Hashimoto (Chugai PharmaceuticalCo Ltd)
3) Comprehensive discussion

Special lectures of the recipients of the 13th
JSIT prize for encouragement

Oral sessions of young scientist“Molecular mechanisms of pathogen sensorsmediated cytokine production from innate
immune cells.”
Izumi Sasaki (Wakayama Medical University)

Oral presentations
Poster presentations
Luncheon seminars
7. Social gathering
Sakagura Dori Rengakan

Workshop: Immunogenicity assessment

4) “Current status and issues in predictionand evaluation of immunogenicity ofbiopharmaceuticals.”
Akiko Ishii (National Institute of HealthSciences)No.1（25）25

September 19, 18:30~ (tentative)
https://www.rengakan.com/index.html

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The 13th Japanese Society of Immunotoxicology Award(The 2023 JSIT Award)
Establishment of a new concept “reproductive immunotoxicity” in immunotoxicology

Kazuichi Nakamura
Translational Research Unit, Veterinary Teaching Hospital,Graduate School of Veterinary Medicine, Hokkaido University
I have been working on creating a new concept “reproductive immunotoxicity” inimmunotoxicology. Here, I would like to briefly explain how pregnancy isimmunologically maintained and to show some xenobiotics which immunotoxicologically
impair the development of placenta and cause abortion.
Fetuses are semi-allogeneic to mothers because they inherit MHC class I genes fromthe father as well as the mother. Since the immune system recognizes and rejects nonself, pregnancy needs specialized immunological mechanism to accept the fetus. In thehemochorial placenta in human and rodents, placental villi directly contact maternal
blood to receive oxygen and nutrient from the mother. The blood flows from remodeled
uterus spiral arteries forming open circulation.
For remodeling of uterus spiral arteries, fetal extravillous trophoblasts (EVTs) entermaternal endometrium in collaboration with uterus NK (uNK) cells, subsequently
decidual NK (dNK) cells. EVTs do not express classical MHC class I molecules HLA-A orHLA-B to avert killing by cytotoxic CD8 T cells. They bear classical MHC class I molecule
HLA-C and nonclassical HLA-E, -F and -G to communicate with uNK cells. uNK cells(CD56brightCD16-) show lower cytotoxic activity in comparison with peripheral blood
NK cells (CD56dim/-CD16bright). uNK/dNK cells also produce angiogenic factors suchas vascular endothelial growth factor (VEGF). Receptors of uNK/dNK cells include killer
cell immunoglobulin-like receptor (KIR), leukocyte immunoglobulin-like receptor (LILR)
and natural killer group 2 (NKG2), each of which has inhibitory and activating
subfamilies. Their cytotoxicity and the production of angiogenic factors depend on thecombination of the EVTs’ MHC class I molecules and the uNK/dNK cell receptors, whichis critical for the placenta formation and fetal growth. To date, there have been someNo.1（26）26

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researches in which Δ9-tetrahydrocannabinol, sphingosine-1-phosphate receptor
modulator or titanium dioxide nanoparticles inhibit healthy placenta formation byaffecting cytotoxicity and angiogenesis of the uNK/dNK cells in human or mice.
Normal pregnancy is associated with high levels of Th2 cytokines and low Th1/Th2
cell ratios. Progesterone produced by corpus stimulate the production of IL-4 from Th2cells. IL-4 increases human chorionic gonadotropin (hCG) from syncytiotrophoblasts offetal villi after implantation for the maintenance of pregnancy. As the consequence, Th2cells are dominant over Th1 cells in the maternal immune system especially during earlypregnancy. From the viewpoint of immunotoxicology, I and my colleagues in the Kitasato
University demonstrated that Th1/Th2 imbalance caused by proteins affects pregnancy.
For more details, please see https://www.jstage.jst.go.jp/article/jts/47/8/47_327/_article.
I think that some causes of recurrent pregnancy loss are attributed to reproductive
immunotoxicity of environmental chemicals and pharmaceuticals. I hope thesexenobiotics exhibiting “reproductive immunotoxicity” will be identified by our society ofimmunotoxicology.
Lastly, but most importantly, I really appreciate the JSIT and SOT ISS members forencouraging my ICH activities and basic researches for almost 30 years. Thank you verymuch.
Thinking about “reproductive immunotoxicity” at;Rurikoin Temple in Kyoto, December 2023

Ryoanji Temple, Rock Garden in Kyoto, March 2024

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The 13th Japanese Society of Immunotoxicology Prize for Encouragement
Immunological mechanisms of metal allergy and its prevention and treatment

Toshinobu Kuroishi
Division of Oral Immunology,
Tohoku University Graduate School of Dentistry
I am deeply honored to have received the 13th JSIT Prize for Encouragement for theyear 2023. I would like to sincerely express my appreciation to Dr. Masashi Tachibana
who recommended me, and to the selection committee members as well as mysupervisors, mentors, and all collaborators.
Metal allergies have been classified as type-IV allergies and induce allergic contact
dermatitis. Nickel (Ni) is the most frequent metal allergen. We previously reported aneffective Ni allergy mouse model with lipopolysaccharide as an adjuvant (Clin. Exp.
Allergy, 2007). Using this mouse model, we have reported the pathological mechanismsof metal allergies. Biotin is a water-soluble B complex vitamin and function as a cofactorof 5 indispensable carboxylases. Biotin deficiency aggravated Ni allergy thorough theaugmentation of IL-1β production (J. Nutr., 2009). Moreover, biotin supplementation indrinking water attenuated Ni allergy, suggesting that biotin supplementation may havetherapeutic effects on metal allergies. We also demonstrated that Ni induces nitric oxide
production in dermal fibroblasts via the HIF-2α-dependent pathway (Tox. Sci., 2013).
Although Ni ion is considered to bind to endogenous proteins, it remains unclear whether
Ni-binding proteins are involved in Ni allergy in vivo. We demonstrated that CXC
chemokine ligand 4 is a novel Ni-binding protein and augments Ni allergy at theelicitation and sensitization phases (Clin. Exp. Allergy, 2017). To understand theunderlying mechanisms by which metal ions are recognized y the immune system, weinvestigated Ni-binding capabilities of antigen-presenting cells, and demonstrated that
migratory dendritic cells in skin-draining lymph nodes have strong Ni-binding
capabilities and elicit Ni allergy (Sci. Rep., 2020).
Encouraged by this award, I will continue my research to develop the effective methods
to prevent and treat metal allergies.
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