RERF Report No. 5-17

Paper published in Radiation Research§“Radiation and Age-associated Changes in Peripheral Blood Dendritic Cell Populations
among Aging Atomic Bomb Survivors in Japan”
Junko Kajimura, Heather E. Lynch, Susan Geyer, Benjamin French, Mika Yamaoka, Ivo D. Shterev,
Gregory D. Sempowski, Seishi Kyoizumi, Kengo Yoshida, Munechika Misumi, Waka Ohishi,
Tomonori Hayashi, Kei Nakachi, Yoichiro Kusunoki
Radiat Res; 189(1):84-94, 2018/1(doi: 10.1667/RR14854.1)
Study Findings
We have examined the relationship of A-bomb radiation exposure with counts and functional
profiles of circulating dendritic cells (DCs), which play an important role in immunological activation.
The results of our study do not indicate any radiation-related change in the number and function ofDCs in the blood of those exposed to radiation from the atomic bombings more than 60 years ago.
Explanation
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Study Purpose
Previous immunological studies of A-bomb survivors have suggested that radiation exposure
accelerates aging of the immune system. However, effects of A-bomb radiation exposure on DCs, key
coordinators for activation and functional differentiation of the immune system, specifically T-cellimmunity, had not yet been examined. This study measured counts and functional profiles ofcirculating conventional DCs (cDCs)* and plasmacytoid DCs (pDCs)** in the peripheral blood of
Adult Health Study (AHS) A-bomb survivor participants to elucidate the relationship of such
numerical and functional changes with radiation dose, sex, and age.
*Conventional dendritic cell (cDC): One of the DC subgroups, cDCs recognize foreign substancesthat invade the body, including pathogens. They present information involving suchforeign substances to other immune cells, including T cells, and thus play a command rolein the eradication of such pathogens.
**Plasmacytoid dendritic cell (pDC): One of the DC subgroups, pDCs are not adept at presenting
information about foreign substances as cDCs; however, pDCs produce large amounts ofvirus-suppressing Type I interferon in response to viral infection.
2.

Study Methods
We collected peripheral blood from 229 A-bomb survivors in Hiroshima who participated in theAHS during the period from 2011 through 2013 (ages 66–91) and measured and separated cDCs andpDCs using a cell sorter. To examine the function of these separated DCs in vitro, we assessed gene
expression levels and cytokine/chemokine* production following Toll-like receptor (TLR)**stimulation.
*Cytokine/chemokine: Cytokines are a broad category of proteins released from cells that play
an important role in biological defense, including immunity and inflammation.
Chemokines are a family of cytokines, and they assist the migration of immune cells tothe site of inflammation.
**Toll-like receptor (TLR): TLRs are sentinel receptors expressing in immune cells such as DCs
and macrophages. TLRs recognize structurally conserved molecules derived frominvading pathogens and promptly activates the innate immune system. (Innate immunity
is a non-specific, inborn immune system that eliminates pathogens regardless of type.)

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3. Study Results(1) Changes in cell counts●Relationship with radiation dose
The absolute number (count per unit volume of blood) of pDCs significantly decreased withincreasing radiation dose only in women (r = -0.17, p = 0.035). There was no significant
association between the absolute number of cDCs and radiation dose in either gender.
●Relationship with age
The absolute numbers of cDCs (r = -0.17, p = 0.033) and pDCs (r = -0.26、p = 0.004)
significantly decreased with age. This decreasing trend was particularly marked in women.
(2) Functional changes●
Relationship with radiation dose
No significant effect of radiation dose was observed in gene expression levels following TLR
stimulation, but inflammatory cytokine/chemokine production levels had a tendency to increase
with radiation dose.
●Relationship with age
Gene expression levels following TLR stimulation significantly decreased with age in cDCs (p =0.048), but no significant effect was observed in pDCs. Furthermore, cytokine/chemokine
production levels following TLR stimulation in cDCs decreased with age.
Study significanceThe present study among AHS participants revealed that human DC counts and functional profiles
continued to decrease even after age 70. It is known that cDCs play a stronger role in the activationof T-cell-mediated immunity than pDCs, but age-related functional decline was observed in cDCs.
The possibility exists that the aging-related decline in T-cell function may be caused by deteriorationin cDC-mediated activation. Furthermore, changes in pDC counts in relation to radiation dose andage were observed in women, but not men suggesting sex differences in the effects of radiation doseand age. Taken together, the counts and functional profiles of DCs circulating in the blood of those
who survived for an extended period after A-bomb radiation exposure generally recovered to normal
levels, i.e., levels typical for the unexposed group of the same generation.
The Radiation Effects Research Foundation has studied A-bomb survivors and their offspring in Hiroshimaand Nagasaki for around 70 years. RERF’s research achievements are considered the principal scientific basis forradiation risk assessment by the United Nations Scientific Committee on the Effects of Atomic Radiation(UNSCEAR) and for recommendations regarding radiation protection standards by the InternationalCommission on Radiological Protection (ICRP). RERF expresses its profound gratitude to the A-bomb survivors
and survivors’ offspring for their cooperation in our studies.
§Radiation Research, which is an official monthly journal of the Radiation Research Society, publishes
original peer-reviewed papers and review articles on radiation effects and related issues in the fields ofphysics, chemistry, biology, and medicine. (Impact factor in 2016/2017: 2.539)

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