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zoom RSS 体内時計が免疫システムを変化させる 夜明けは感染に弱い

<<   作成日時 : 2012/02/21 20:16   >>

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画像体内時計が免疫システムを変化させる
 米国での研究によれば、1日のうちの時間が感染のリスクの重要な因子となるという。
体内の化学物質の日内変動により免疫系のタンパク質が影響を受け、感染の時間により重症度が変化したという。
 イェール大学医学部の研究者によれば、免疫システムが戦いを開始する前に感染を検出する必要があり、細菌やウイルスのDNAがくっつくToll様受容体9(TLR9)という検出プロセスに関与するタンパク質を調査していた。
 マウスの実験では、作られるTLR9量とその作法は体内時計に制御された日内変動があることがわかった。TLR9量がピーク時には免疫反応が改善している。
 敗血症、敗血症の人の死亡リスクが午前2時と6時の間に高いことが知られていたという。

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17 February 2012 Last updated at 01:43 GMT
Body clock 'alters' immune system
By James Gallagher
Health and science reporter, BBC News
http://www.bbc.co.uk/news/health-17059498

The time of the day could be an important factor in the risk of getting an infection, according to researchers in the US.

They showed how a protein in the immune system was affected by changes in the chemistry of the body through the day.

The findings, published in the journal Immunity, showed the time of an infection changed its severity.

An expert said drugs were likely to take advantage of the body clock in the near future.

Plants, animals and even bacteria go through a daily 24-hour routine, known as a circadian rhythm. Jet lag is what happens when the body gets out of sync with its surroundings after crossing time zones.

It has been known that there are variations in the immune system throughout the day. Researchers are now drilling down into the details.

The immune system needs to detect an infection before it can begin to fight it off. Researchers at Yale University School of Medicine were investigating one of the proteins involved in the detection process - Toll-like receptor nine (TLR9), which can spot DNA from bacteria and viruses.

In experiments on mice, the scientists showed that the amount of TLR9 produced and the way it functioned was controlled by the body clock and varied through the day.

Immunising mice at the peak of TLR9 activity improved the immune response, the researchers said.

They said humans with sepsis, blood poisoning, were known to be at a greater risk of death between 02:00 and 06:00.

Time link
When testing mice, the severity of sepsis depended on the time of day infection started and coincided with changes in TLR9 activity.

Prof Erol Fikrig, who conducted the study at Yale University, said they had found a "direct molecular link between circadian rhythms and the immune system", which could have "important implications for the prevention and treatment of disease".

He added: "It does appear that disruptions of the circadian clock influence our susceptibility to pathogens."

Dr Akhilesh Reddy, who is researching circadian rhythms at the University of Cambridge, said it was "known long ago" that timing had an impact on the immune system, but this was "one of the first forays" into the reasons why.

The implications for healthcare could mean that drugs need to be given at certain times of day in order to make them more effective, or drugs could be made which actually target the body clock to put the immune system into its most active phase.

Dr Reddy said drug companies were "all switching onto this" and were "now screening drugs at different times of the day".

He could see the body clock impacting medicine "within 10 years".

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The Circadian Clock Controls Toll-like Receptor 9-Mediated Innate and Adaptive Immunity

Immunity, 16 February 2012
Copyright c 2012 Elsevier Inc. All rights reserved.
10.1016/j.immuni.2011.12.017

Authors
Adam C. Silver, Alvaro Arjona, Wendy E. Walker, Erol FikrigSee Affiliations
Highlights
The circadian molecular clock modulates Tlr9 expression and function
There are in vivo daily variations in the responsiveness to CpG ODNs (TLR9 ligand)
The time of day determines disease severity in a TLR9-dependent sepsis model
Timing of immunization determines TLR9 ligand-adjuvanted vaccine responsiveness
Summary

Circadian rhythms refer to biologic processes that oscillate with a period of ?24 hr. These rhythms are sustained by a molecular clock and provide a temporal matrix that ensures the coordination of homeostatic processes with the periodicity of environmental challenges. We demonstrate the circadian molecular clock controls the expression and function of Toll-like receptor 9 (TLR9). In a vaccination model using TLR9 ligand as adjuvant, mice immunized at the time of enhanced TLR9 responsiveness presented weeks later with an improved adaptive immune response. In a TLR9-dependent mouse model of sepsis, we found that disease severity was dependent on the timing of sepsis induction, coinciding with the daily changes in TLR9 expression and function. These findings unveil a direct molecular link between the circadian and innate immune systems with important implications for immunoprophylaxis and immunotherapy.

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