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Written by | My best friend, the old Red Riding Hood’s brain, has attracted more and more attention to the regulation of the immune system
.
The current work focuses on the following aspects, one is under pressure [1], the other is stroke [2], and the third is reward and punishment feedback system [3, 4]
.
Of course, the academic research on this aspect is still very limited, and, most importantly, so far, the way and degree of the brain through which the body's inflammatory state is apparent is still unknown
.
On November 8, 2021, the Asya Rolls research group from Israel published an article titled Insular cortex neurons encode and retrieve specific immune responses on Cell.
It was found that neurons distributed in the insular lobe of the mouse brain will be activated under inflammation.
, Thereby regulating the peripheral immune response
.
From the following multiple evidences, it can be inferred that the brain is likely to receive signals from the body's immune system, and to characterize and feed back this signal
.
First, from anatomically speaking, peripheral immune organs can transmit information to the brain through sensory neurons [5, 6]; second, from the perspective of brain science, through brain imaging technology, when inflammation occurs in the peripheral immune system, more Several brain regions, including the amygdala, hypothalamus, brainstem, thalamus and insular cortex, will respond [7]
.
In addition, it has been reported that some brain areas, such as the insular cortex, are closely related to immune response [8]
.
Based on the above work, the authors constructed a DSS-induced mouse enteritis model and found that in an inflammatory state, brain neurons are activated, specifically in the brain region, the insular cortex neurons are highly activated after enteritis in the mouse, and these activated neurons Of these, 71% are glutamatergic neurons and 20% are GABAergic neurons
.
This shows that enteritis is related to the activation of insular cortex neurons, but it cannot be said that these neurons can specifically characterize the body's immune system status
.
In order to further study the relationship between neuronal activation and enteritis, the author reactivated the insular cortex neurons by overexpression of neuron activator during the recovery period of mice with enteritis, and detected related indicators of the intestinal immune system, and found that even if Without the control group induced by DSS, stimulating neurons can significantly improve the intestinal immune response
.
Specifically, the level of white blood cells in the mucosal layer of the intestine increased significantly, the level of activated CD4+ T cells and CD8+ T cells increased, and the level of dendritic cells involved in T cell activation also increased significantly
.
Further analysis determined that the levels of CD4+ T cells expressing the inflammatory factor IL-6 and TNF-a monocytes also increased significantly
.
In addition, the authors also found that these obvious inflammatory states basically only occur in the intestines, while the levels of immune cells in peripheral blood and lymph nodes have not changed significantly
.
These results indicate that the activation state of brain neurons can also affect the state of peripheral inflammation
.
In addition, the author obtained similar results in a mouse peritonitis model induced by zymosan
.
Next, the author studies the anatomical basis of information transmission between the insular cortex of the brain and the intestine
.
The author used the method of injecting pseudorabies virus linked with immunofluorescent protein into mice, marking the nerve signal transmission method, and found that peripheral inflammation signals can be transmitted to the brain through the autonomic nervous system
.
Finally, the authors investigated whether specific inhibition of cerebral insular cortex neurons can also affect peripheral inflammation
.
The author found through the method of overexpression of neuron inhibitors that inhibiting neurons can alleviate the various clinical symptoms of DSS-induced mice, such as the length of the large intestine and the weight of the spleen; however, some other clinical indicators have little change in pathological indicators
.
Of course, after inhibiting neurons, the number and proportion of intestinal immune cells are reduced, including the aforementioned IL-6+T cells and so on
.
These results indicate that inhibition of the cerebral insular cortex can alleviate some of the clinical indicators and immunological response indicators of enteritis
.
In summary, the authors determined that the cerebral insular cortex can receive immune signals, and both the DSS-induced enteritis model and the zymosan-induced peritonitis model can activate the cerebral insular cortex neurons
.
The author also determined that the autonomic nervous system is the anatomical basis of this process
.
Finally, the authors found that inhibiting cerebral insular cortex neurons can relieve the symptoms of enteritis in mice to a certain extent, which also indicates that regulating neurons is likely to be a feasible method for the treatment of peripheral inflammation
.
Original link: https://doi.
org/10.
1016/j.
cell.
2021.
10.
013 Platemaker: Eleven References [1] Chovatiya, R.
, and Medzhitov, R.
(2014).
Stress, inflammation, and defense of homeostasis.
Mol.
Cell 54, 281–288.
[2] Wong, CHY, Jenne, CN, Lee, W.
-Y.
, Le ́ ger, C.
, and Kubes, P.
(2011).
Func- tional innervation of hepatic iNKT cells is immunosuppressive following stroke.
Science 334, 101–105.
[3] Ben-Shaanan, TL, Azulay-Debby, H.
, Dubovik, T.
, Starosvetsky, E.
, Korin, B.
, Schiller, M.
, Green, NL, Admon, Y.
, Hakim, F.
, Shen-Orr, SS, and Rolls, A.
(2016).
Activation of the reward system boosts innate and adaptive immunity.
Nat.
Med.
22, 940 –944.
[4] Ben-Shaanan, TL, Schiller, M.
, Azulay-Debby, H.
, Korin, B.
, Boshnak, N.
, Koren, T.
, Krot, M.
, Shakya, J.
, Rahat , MA, Hakim, F.
, and Rolls, A.
(2018).
Modulation of anti-tumor immunity by the brain's reward system.
Nat.
Commun.
9,2723.
[5] Pavlov, VA, and Tracey, KJ (2017).
Neural regulation of immunity: molecular mechanisms and clinical translation.
Nat.
Neurosci.
20, 156–166.
[6] Dantzer, R.
(2018).
Neuroimmune Interactions: From the brain to the immune system and vice versa.
Physiol.
Rev.
98, 477–504.
[7] Sergeeva, M.
, Rech, J.
, Schett, G.
, and Hess, A.
(2015).
Response to periph- eral immune stimulation within the brain: magnetic resonance imaging perspective of treatment success.
Arthritis Res.
Ther.
17, 268.
【8】Ramı ́rez-Amaya, V.
, Alvarez-Borda, B.
, Ormsby, CE, Martı ́nez, RD, Pe ́ rez- Montfort, R.
, and Bermu ́ dez-Rattoni, F.
(1996).
Insular cortex lesions impair the acquisition of conditioned immunosuppression.
Brain Behav.
Immun.
10, 103–114.
[Original Articles] BioArt original articles, personal reposting and sharing are welcome, reprinting is prohibited without permission, the copyrights of all published works are owned by BioArtNeural regulation of immunity: molecular mechanisms and clinical translation.
Nat.
Neurosci.
20, 156–166.
[6] Dantzer, R.
(2018).
Neuroimmune interactions: From the brain to the immune system and vice versa.
Physiol.
Rev.
98, 477–504.
[7] Sergeeva, M.
, Rech, J.
, Schett, G.
, and Hess, A.
(2015).
Response to periph- eral immune stimulation within the brain: magnetic resonance imaging perspective of treatment success.
Arthritis Res.
Ther.
17, 268.
【8】Ramı ́rez-Amaya, V.
, Alvarez-Borda, B.
, Ormsby, CE, Martı ́nez, RD, Pe ́ rez- Montfort, R.
, and Bermu ́ dez-Rattoni, F.
(1996).
Insular cortex lesions impair the acquisition of conditioned immunosuppression.
Brain Behav.
Immun.
10, 103–114.
Instructions for reprinting 【Original Articles】BioArt original articles, personal forwarding and sharing are welcome, and it is prohibited without permission Reprinted, the copyrights of all published works are owned by BioArtNeural regulation of immunity: molecular mechanisms and clinical translation.
Nat.
Neurosci.
20, 156–166.
[6] Dantzer, R.
(2018).
Neuroimmune interactions: From the brain to the immune system and vice versa.
Physiol.
Rev.
98, 477–504.
[7] Sergeeva, M.
, Rech, J.
, Schett, G.
, and Hess, A.
(2015).
Response to periph- eral immune stimulation within the brain: magnetic resonance imaging perspective of treatment success.
Arthritis Res.
Ther.
17, 268.
【8】Ramı ́rez-Amaya, V.
, Alvarez-Borda, B.
, Ormsby, CE, Martı ́nez, RD, Pe ́ rez- Montfort, R.
, and Bermu ́ dez-Rattoni, F.
(1996).
Insular cortex lesions impair the acquisition of conditioned immunosuppression.
Brain Behav.
Immun.
10, 103–114.
Instructions for reprinting 【Original Articles】BioArt original articles, personal forwarding and sharing are welcome, and it is prohibited without permission Reprinted, the copyrights of all published works are owned by BioArt(2018).
Neuroimmune interactions: From the brain to the immune system and vice versa.
Physiol.
Rev.
98, 477–504.
[7] Sergeeva, M.
, Rech, J.
, Schett, G.
, and Hess, A .
(2015).
Response to periph- eral immune stimulation within the brain: magnetic resonance imaging perspective of treatment success.
Arthritis Res.
Ther.
17, 268.
【8】Ramı ́rez-Amaya, V.
, Alvarez-Borda, B.
, Ormsby, CE, Martı ́nez, RD, Pe ́ rez- Montfort, R.
, and Bermu ́ dez-Rattoni, F.
(1996).
Insular cortex lesions impair the acquisition of conditioned immunosuppression.
Brain Behav.
Immun.
10, 103 –114.
Reprinting instructions [Original Articles] BioArt original articles, personal reposting and sharing are welcome, reprinting is prohibited without permission, the copyright of all published works is owned by BioArt(2018).
Neuroimmune interactions: From the brain to the immune system and vice versa.
Physiol.
Rev.
98, 477–504.
[7] Sergeeva, M.
, Rech, J.
, Schett, G.
, and Hess, A .
(2015).
Response to periph- eral immune stimulation within the brain: magnetic resonance imaging perspective of treatment success.
Arthritis Res.
Ther.
17, 268.
【8】Ramı ́rez-Amaya, V.
, Alvarez-Borda, B.
, Ormsby, CE, Martı ́nez, RD, Pe ́ rez- Montfort, R.
, and Bermu ́ dez-Rattoni, F.
(1996).
Insular cortex lesions impair the acquisition of conditioned immunosuppression.
Brain Behav.
Immun.
10, 103 –114.
Reprinting instructions [Original Articles] BioArt original articles, personal reposting and sharing are welcome, reprinting is prohibited without permission, the copyright of all published works is owned by BioArtResponse to periph- eral immune stimulation within the brain: magnetic resonance imaging perspective of treatment success.
Arthritis Res.
Ther.
17, 268.
【8】Ramı ́rez-Amaya, V.
, Alvarez-Borda, B.
, Ormsby, CE, Martı ́nez, RD, Pe ́ rez- Montfort, R.
, and Bermu ́ dez-Rattoni, F.
(1996).
Insular cortex lesions impair the acquisition of conditioned immunosuppression.
Brain Behav.
Immun.
10, 103–114.
[Original Articles] BioArt original articles, personal reposting and sharing are welcome, reprinting is prohibited without permission, the copyrights of all published works are owned by BioArtResponse to periph- eral immune stimulation within the brain: magnetic resonance imaging perspective of treatment success.
Arthritis Res.
Ther.
17, 268.
【8】Ramı ́rez-Amaya, V.
, Alvarez-Borda, B.
, Ormsby, CE, Martı ́nez, RD, Pe ́ rez- Montfort, R.
, and Bermu ́ dez-Rattoni, F.
(1996).
Insular cortex lesions impair the acquisition of conditioned immunosuppression.
Brain Behav.
Immun.
10, 103–114.
[Original Articles] BioArt original articles, personal reposting and sharing are welcome, reprinting is prohibited without permission, the copyrights of all published works are owned by BioArtReprinting Instructions [Original Articles] BioArt original articles are welcome to be shared by individuals.
Reprinting is prohibited without permission.
The copyrights of all published works are owned by BioArtReprinting Instructions [Original Articles] BioArt original articles are welcome to be shared by individuals.
Reprinting is prohibited without permission.
The copyrights of all published works are owned by BioArt
.
BioArt reserves all statutory rights and offenders must be investigated
.
.
The current work focuses on the following aspects, one is under pressure [1], the other is stroke [2], and the third is reward and punishment feedback system [3, 4]
.
Of course, the academic research on this aspect is still very limited, and, most importantly, so far, the way and degree of the brain through which the body's inflammatory state is apparent is still unknown
.
On November 8, 2021, the Asya Rolls research group from Israel published an article titled Insular cortex neurons encode and retrieve specific immune responses on Cell.
It was found that neurons distributed in the insular lobe of the mouse brain will be activated under inflammation.
, Thereby regulating the peripheral immune response
.
From the following multiple evidences, it can be inferred that the brain is likely to receive signals from the body's immune system, and to characterize and feed back this signal
.
First, from anatomically speaking, peripheral immune organs can transmit information to the brain through sensory neurons [5, 6]; second, from the perspective of brain science, through brain imaging technology, when inflammation occurs in the peripheral immune system, more Several brain regions, including the amygdala, hypothalamus, brainstem, thalamus and insular cortex, will respond [7]
.
In addition, it has been reported that some brain areas, such as the insular cortex, are closely related to immune response [8]
.
Based on the above work, the authors constructed a DSS-induced mouse enteritis model and found that in an inflammatory state, brain neurons are activated, specifically in the brain region, the insular cortex neurons are highly activated after enteritis in the mouse, and these activated neurons Of these, 71% are glutamatergic neurons and 20% are GABAergic neurons
.
This shows that enteritis is related to the activation of insular cortex neurons, but it cannot be said that these neurons can specifically characterize the body's immune system status
.
In order to further study the relationship between neuronal activation and enteritis, the author reactivated the insular cortex neurons by overexpression of neuron activator during the recovery period of mice with enteritis, and detected related indicators of the intestinal immune system, and found that even if Without the control group induced by DSS, stimulating neurons can significantly improve the intestinal immune response
.
Specifically, the level of white blood cells in the mucosal layer of the intestine increased significantly, the level of activated CD4+ T cells and CD8+ T cells increased, and the level of dendritic cells involved in T cell activation also increased significantly
.
Further analysis determined that the levels of CD4+ T cells expressing the inflammatory factor IL-6 and TNF-a monocytes also increased significantly
.
In addition, the authors also found that these obvious inflammatory states basically only occur in the intestines, while the levels of immune cells in peripheral blood and lymph nodes have not changed significantly
.
These results indicate that the activation state of brain neurons can also affect the state of peripheral inflammation
.
In addition, the author obtained similar results in a mouse peritonitis model induced by zymosan
.
Next, the author studies the anatomical basis of information transmission between the insular cortex of the brain and the intestine
.
The author used the method of injecting pseudorabies virus linked with immunofluorescent protein into mice, marking the nerve signal transmission method, and found that peripheral inflammation signals can be transmitted to the brain through the autonomic nervous system
.
Finally, the authors investigated whether specific inhibition of cerebral insular cortex neurons can also affect peripheral inflammation
.
The author found through the method of overexpression of neuron inhibitors that inhibiting neurons can alleviate the various clinical symptoms of DSS-induced mice, such as the length of the large intestine and the weight of the spleen; however, some other clinical indicators have little change in pathological indicators
.
Of course, after inhibiting neurons, the number and proportion of intestinal immune cells are reduced, including the aforementioned IL-6+T cells and so on
.
These results indicate that inhibition of the cerebral insular cortex can alleviate some of the clinical indicators and immunological response indicators of enteritis
.
In summary, the authors determined that the cerebral insular cortex can receive immune signals, and both the DSS-induced enteritis model and the zymosan-induced peritonitis model can activate the cerebral insular cortex neurons
.
The author also determined that the autonomic nervous system is the anatomical basis of this process
.
Finally, the authors found that inhibiting cerebral insular cortex neurons can relieve the symptoms of enteritis in mice to a certain extent, which also indicates that regulating neurons is likely to be a feasible method for the treatment of peripheral inflammation
.
Original link: https://doi.
org/10.
1016/j.
cell.
2021.
10.
013 Platemaker: Eleven References [1] Chovatiya, R.
, and Medzhitov, R.
(2014).
Stress, inflammation, and defense of homeostasis.
Mol.
Cell 54, 281–288.
[2] Wong, CHY, Jenne, CN, Lee, W.
-Y.
, Le ́ ger, C.
, and Kubes, P.
(2011).
Func- tional innervation of hepatic iNKT cells is immunosuppressive following stroke.
Science 334, 101–105.
[3] Ben-Shaanan, TL, Azulay-Debby, H.
, Dubovik, T.
, Starosvetsky, E.
, Korin, B.
, Schiller, M.
, Green, NL, Admon, Y.
, Hakim, F.
, Shen-Orr, SS, and Rolls, A.
(2016).
Activation of the reward system boosts innate and adaptive immunity.
Nat.
Med.
22, 940 –944.
[4] Ben-Shaanan, TL, Schiller, M.
, Azulay-Debby, H.
, Korin, B.
, Boshnak, N.
, Koren, T.
, Krot, M.
, Shakya, J.
, Rahat , MA, Hakim, F.
, and Rolls, A.
(2018).
Modulation of anti-tumor immunity by the brain's reward system.
Nat.
Commun.
9,2723.
[5] Pavlov, VA, and Tracey, KJ (2017).
Neural regulation of immunity: molecular mechanisms and clinical translation.
Nat.
Neurosci.
20, 156–166.
[6] Dantzer, R.
(2018).
Neuroimmune Interactions: From the brain to the immune system and vice versa.
Physiol.
Rev.
98, 477–504.
[7] Sergeeva, M.
, Rech, J.
, Schett, G.
, and Hess, A.
(2015).
Response to periph- eral immune stimulation within the brain: magnetic resonance imaging perspective of treatment success.
Arthritis Res.
Ther.
17, 268.
【8】Ramı ́rez-Amaya, V.
, Alvarez-Borda, B.
, Ormsby, CE, Martı ́nez, RD, Pe ́ rez- Montfort, R.
, and Bermu ́ dez-Rattoni, F.
(1996).
Insular cortex lesions impair the acquisition of conditioned immunosuppression.
Brain Behav.
Immun.
10, 103–114.
[Original Articles] BioArt original articles, personal reposting and sharing are welcome, reprinting is prohibited without permission, the copyrights of all published works are owned by BioArtNeural regulation of immunity: molecular mechanisms and clinical translation.
Nat.
Neurosci.
20, 156–166.
[6] Dantzer, R.
(2018).
Neuroimmune interactions: From the brain to the immune system and vice versa.
Physiol.
Rev.
98, 477–504.
[7] Sergeeva, M.
, Rech, J.
, Schett, G.
, and Hess, A.
(2015).
Response to periph- eral immune stimulation within the brain: magnetic resonance imaging perspective of treatment success.
Arthritis Res.
Ther.
17, 268.
【8】Ramı ́rez-Amaya, V.
, Alvarez-Borda, B.
, Ormsby, CE, Martı ́nez, RD, Pe ́ rez- Montfort, R.
, and Bermu ́ dez-Rattoni, F.
(1996).
Insular cortex lesions impair the acquisition of conditioned immunosuppression.
Brain Behav.
Immun.
10, 103–114.
Instructions for reprinting 【Original Articles】BioArt original articles, personal forwarding and sharing are welcome, and it is prohibited without permission Reprinted, the copyrights of all published works are owned by BioArtNeural regulation of immunity: molecular mechanisms and clinical translation.
Nat.
Neurosci.
20, 156–166.
[6] Dantzer, R.
(2018).
Neuroimmune interactions: From the brain to the immune system and vice versa.
Physiol.
Rev.
98, 477–504.
[7] Sergeeva, M.
, Rech, J.
, Schett, G.
, and Hess, A.
(2015).
Response to periph- eral immune stimulation within the brain: magnetic resonance imaging perspective of treatment success.
Arthritis Res.
Ther.
17, 268.
【8】Ramı ́rez-Amaya, V.
, Alvarez-Borda, B.
, Ormsby, CE, Martı ́nez, RD, Pe ́ rez- Montfort, R.
, and Bermu ́ dez-Rattoni, F.
(1996).
Insular cortex lesions impair the acquisition of conditioned immunosuppression.
Brain Behav.
Immun.
10, 103–114.
Instructions for reprinting 【Original Articles】BioArt original articles, personal forwarding and sharing are welcome, and it is prohibited without permission Reprinted, the copyrights of all published works are owned by BioArt(2018).
Neuroimmune interactions: From the brain to the immune system and vice versa.
Physiol.
Rev.
98, 477–504.
[7] Sergeeva, M.
, Rech, J.
, Schett, G.
, and Hess, A .
(2015).
Response to periph- eral immune stimulation within the brain: magnetic resonance imaging perspective of treatment success.
Arthritis Res.
Ther.
17, 268.
【8】Ramı ́rez-Amaya, V.
, Alvarez-Borda, B.
, Ormsby, CE, Martı ́nez, RD, Pe ́ rez- Montfort, R.
, and Bermu ́ dez-Rattoni, F.
(1996).
Insular cortex lesions impair the acquisition of conditioned immunosuppression.
Brain Behav.
Immun.
10, 103 –114.
Reprinting instructions [Original Articles] BioArt original articles, personal reposting and sharing are welcome, reprinting is prohibited without permission, the copyright of all published works is owned by BioArt(2018).
Neuroimmune interactions: From the brain to the immune system and vice versa.
Physiol.
Rev.
98, 477–504.
[7] Sergeeva, M.
, Rech, J.
, Schett, G.
, and Hess, A .
(2015).
Response to periph- eral immune stimulation within the brain: magnetic resonance imaging perspective of treatment success.
Arthritis Res.
Ther.
17, 268.
【8】Ramı ́rez-Amaya, V.
, Alvarez-Borda, B.
, Ormsby, CE, Martı ́nez, RD, Pe ́ rez- Montfort, R.
, and Bermu ́ dez-Rattoni, F.
(1996).
Insular cortex lesions impair the acquisition of conditioned immunosuppression.
Brain Behav.
Immun.
10, 103 –114.
Reprinting instructions [Original Articles] BioArt original articles, personal reposting and sharing are welcome, reprinting is prohibited without permission, the copyright of all published works is owned by BioArtResponse to periph- eral immune stimulation within the brain: magnetic resonance imaging perspective of treatment success.
Arthritis Res.
Ther.
17, 268.
【8】Ramı ́rez-Amaya, V.
, Alvarez-Borda, B.
, Ormsby, CE, Martı ́nez, RD, Pe ́ rez- Montfort, R.
, and Bermu ́ dez-Rattoni, F.
(1996).
Insular cortex lesions impair the acquisition of conditioned immunosuppression.
Brain Behav.
Immun.
10, 103–114.
[Original Articles] BioArt original articles, personal reposting and sharing are welcome, reprinting is prohibited without permission, the copyrights of all published works are owned by BioArtResponse to periph- eral immune stimulation within the brain: magnetic resonance imaging perspective of treatment success.
Arthritis Res.
Ther.
17, 268.
【8】Ramı ́rez-Amaya, V.
, Alvarez-Borda, B.
, Ormsby, CE, Martı ́nez, RD, Pe ́ rez- Montfort, R.
, and Bermu ́ dez-Rattoni, F.
(1996).
Insular cortex lesions impair the acquisition of conditioned immunosuppression.
Brain Behav.
Immun.
10, 103–114.
[Original Articles] BioArt original articles, personal reposting and sharing are welcome, reprinting is prohibited without permission, the copyrights of all published works are owned by BioArtReprinting Instructions [Original Articles] BioArt original articles are welcome to be shared by individuals.
Reprinting is prohibited without permission.
The copyrights of all published works are owned by BioArtReprinting Instructions [Original Articles] BioArt original articles are welcome to be shared by individuals.
Reprinting is prohibited without permission.
The copyrights of all published works are owned by BioArt
.
BioArt reserves all statutory rights and offenders must be investigated
.
