TY - JOUR
T1 - Insight into innate immune response in “Yusho”
T2 - The impact of natural killer cell and regulatory T cell on inflammatory prone diathesis of Yusho patients
AU - Kamio, Yoshiyuki
AU - Gunge, Yumi
AU - Koike, Yuta
AU - Kuwatsuka, Yutaka
AU - Tsuruta, Kazuto
AU - Yanagihara, Katsunori
AU - Furue, Masutaka
AU - Murota, Hiroyuki
N1 - Funding Information:
This work was supported by a grant from The Ministry of Health, Labour, and Welfare in Japan ( H30-Shokuhin-Shitei-005 ). The study protocol was approved by the Japanese Ministry of Health, Labor, and Welfare and the Kyushu University Institutional Review Board for Clinical Research (approval no. 30–384).
Funding Information:
This work was supported by a grant from The Ministry of Health, Labour, and Welfare in Japan (H30-Shokuhin-Shitei-005). The study protocol was approved by the Japanese Ministry of Health, Labor, and Welfare and the Kyushu University Institutional Review Board for Clinical Research (approval no. 30?384).
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/6
Y1 - 2020/6
N2 - Background: In 1968 in western Japan, polychlorinated biphenyl-contaminated “Kanemi rice oil” was used in cooking, causing food poisoning in many people. More than 50 years have passed since the Yusho incident, and although inflammatory disorders such as suppuration have been observed in Yusho patients, the etiology of this inflammation susceptibility remains obscure. Objectives: To investigate the mechanisms of susceptibility to inflammation in Yusho patients, peripheral immune cell fractions and concentrations of inflammatory cytokines were evaluated in blood samples collected from both Yusho patients and age-matched healthy subjects undergoing medical examination in Nagasaki. Methods: To exclude diagnostic uncertainty, serum levels of polychlorinated biphenyl (PCB), polychlorinated quarterphenyl (PCQ), and polychlorinated dibenzofuran (PCDF) were measured. Immune cell (e.g. natural killer and regulatory T cell) populations were analyzed by flow cytometry. Serum cytokines involved in immune cell activation were measured by ELISA. Results: The relative proportion of natural killer cells was higher in Yusho patients than in healthy subjects, while the proportion of regulatory T cells did not differ between groups. Serum concentrations of IL-36 and IFN-γ were significantly lower in Yusho patients than in healthy subjects. Conversely, serum cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), which is a cytokine related to activated NK cells, was higher in Yusho patients than in healthy subjects and was positively correlated with PCDF blood levels. Conclusion: Increased numbers of NK cells in Yusho patients suggests that the innate immune response has been activated in Yusho patients. The seemingly paradoxical results for CTLA-4 and IFN-γ may reflect counterbalancing mechanisms preventing excessive NK cell activation. This dysregulation of innate immunity might contribute to the inflammation observed in Yusho patients.
AB - Background: In 1968 in western Japan, polychlorinated biphenyl-contaminated “Kanemi rice oil” was used in cooking, causing food poisoning in many people. More than 50 years have passed since the Yusho incident, and although inflammatory disorders such as suppuration have been observed in Yusho patients, the etiology of this inflammation susceptibility remains obscure. Objectives: To investigate the mechanisms of susceptibility to inflammation in Yusho patients, peripheral immune cell fractions and concentrations of inflammatory cytokines were evaluated in blood samples collected from both Yusho patients and age-matched healthy subjects undergoing medical examination in Nagasaki. Methods: To exclude diagnostic uncertainty, serum levels of polychlorinated biphenyl (PCB), polychlorinated quarterphenyl (PCQ), and polychlorinated dibenzofuran (PCDF) were measured. Immune cell (e.g. natural killer and regulatory T cell) populations were analyzed by flow cytometry. Serum cytokines involved in immune cell activation were measured by ELISA. Results: The relative proportion of natural killer cells was higher in Yusho patients than in healthy subjects, while the proportion of regulatory T cells did not differ between groups. Serum concentrations of IL-36 and IFN-γ were significantly lower in Yusho patients than in healthy subjects. Conversely, serum cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), which is a cytokine related to activated NK cells, was higher in Yusho patients than in healthy subjects and was positively correlated with PCDF blood levels. Conclusion: Increased numbers of NK cells in Yusho patients suggests that the innate immune response has been activated in Yusho patients. The seemingly paradoxical results for CTLA-4 and IFN-γ may reflect counterbalancing mechanisms preventing excessive NK cell activation. This dysregulation of innate immunity might contribute to the inflammation observed in Yusho patients.
UR - http://www.scopus.com/inward/record.url?scp=85082417248&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85082417248&partnerID=8YFLogxK
U2 - 10.1016/j.envres.2020.109415
DO - 10.1016/j.envres.2020.109415
M3 - Article
C2 - 32240844
AN - SCOPUS:85082417248
SN - 0013-9351
VL - 185
JO - Environmental Research
JF - Environmental Research
M1 - 109415
ER -