Cell review deep interpretation of interleukin-17: a mysterious social cytokine!

May 28, 2020 /
Bio-Valley
BIOON/ -- In a recent review entitled "Interleukin-17: A Social Cytokine" published in the international journalCell
, scientists from GeneTek, USA, discussed social cytokines called Interleukin-17Some children with autism spectrum disorder (ASD) show improvement in body behavior when they develop inflammation-associated fever, but researchers know little about the mechanisms; in a recent study published in the journal Nature, researcher Reed et alfound that the production of leukoid-17 (IL-17) in the process of inflammation promotes social behavior in mouse models of neurodevelopmental disordersPicture: Casper CHoogenraad, et al.
Cell
doi:10.1016/j.cell.2020.03.060Over the past few decades, we have learned that a short period of time in the mother's womb may affect an individual's overall health in later life; Influence, recent studies have shown that maternal immune activation (MIA, maternal immune), and in particular leukade-17 (IL-17), are a key factor in promoting neurodevelopmental abnormalities in the offspring of mice; It depends on when it occurs, whether at the embryonic stage or in the early stages of adulthoodNow, researchers are usinggeneticand environmental models of neurodevelopmental disorders in mice, and now they are the first to find that systemic inflammation and il-17 production can save the body's social behavioral defects by directly affecting the brain's neuroactivityresearchers first used lipid polysaccharides (LPS) to simulate the rise in body temperature associated with infection to explore mechanisms for saving social behavioral defects associated with fever, and LPS was able to temporarily save the social behavior measured by the three-room social behavior test in MIA offspring (not against the offspring), a social capability measurement that measures the cost of investigating a social object (the same male) and an inanimate object The percentage of time; the researchers were able to observe LPS-induced savings in young and elderly mouse bodies, suggesting that this may be a common phenomenon and not limited to early adulthood, however, the genetic
engineered mouse model (GEMMs) used to study social disorders did not benefit from LPS therapy, and the researchers then delved into the key role of fever itself in observed behavioral salvation They found that regulating the hypothalamus neural circuits responsible for inducing body temperature rise did not promote social behavioral preferences for MIA offspring without systemic inflammation, and studies suggest that acute fever itself may not be the primary driver of LPS-induced salvation previous researchers have confirmed that adult MIA offspring will exhibit certain cortical abnormalities, which will be prioritized in the granularization of areas including the main cortical cortex region (S1DZ), which will mediate MIA-induced behavioral abnormalities, compared with the control group, the increase in the number of Fos-plus active neurons in S1DZ may be a feature of the cerebral cortex phenothyme, S1DZ neuroactivity reduction can greatly save the induced MIA induced abnormal The lack of social behavior in the body, consistent with the results, MIA offspring in LPS treatment after S1DZ neuroactivity will decline; Local inhibition of neuronal activity in S1DZ saves the social behavioural defects of GEEMs individuals, similar to the descendants of MIA, and the results suggest that changes in cortical activity are a common mechanism for controlling the environment and the social behavior of the genetic of mouse models Picture: Casper C Hoogenraad, et al.
Cell
doi:10.1016/j.cell.2020.03.060 The main problem at present is how systemic LPS affects the neural activity of the central nervous system, and LPS increases the production of a large number of inflammatory cytokines, including IFN, IL-6, TNF-and IL-7, and it is worth noting that IL-17 is the only significant upward cell factor in the medgena in the offspring of MIA, which is again controlled or controlled in mice In addition, the receptor subunit (IL17RA) of IL-17 is expressed in the cortical neurons of S1DZ, suggesting that THE level of IL-17 will rise after LPS treatment, which may directly reduce the brain's neural activity, thus restoring the body's social behavior, and in addition, the direct giving of recombinant IL-17 in S1DZ is sufficient to increase the social behavior of MIA progenitors and GEMMs The results show that IL-17 will save the body's social behavior by the original cause of overactivity of S1DZ neurons, while IL-17a has also been shown to act directly on neurons to regulate the reaction of the beautiful hidden bar nematodes, then IL-17 alone can mediate THE behavior saved by LPS-driven behavior? To answer this question, the researchers found that how anti-IL-17 blocking antibodies and IL17RA knock-out mice inhibited the social savings induced by LPS, providing convincing evidence of the leading role of the IL-17 pathway in the social behavior of MIA offspring mice The researchers revealed the correlation between the close relationship between the nervous system and the immune system, while extensive discussions were held on future therapeutic measures to treat neurodevelopmental disorders, targeting the activity of IL17RA-neurons in S1DZ or helping to develop new therapies to treat ASD-related behavioral symptoms, and recombinant IL17 may also be a potential target for the development of therapeutic interventions for neurodevelopmental disorders However, intervention in the IL17/IL17RA signaling pathway in human organisms may be associated with an increased risk of suicide, which may present some difficulty in revealing complex human behavior, and other studies that understand the characteristics of the IL17/IL17RA pathway in neurodevelopmental disorders may also help identify patients whose symptoms may improve after exposure to IL-17 Another issue to consider for the development of new interventions in the future is that LPS-mediated social rescue behavior disappears 72 hours after treatment; in this case, researchers may consider a gene therapy method, in which IL-17 is transported locally in the central nervous system, which may bypass persistence but may not require safe signals Finally, the researchers said, the results of this paper may provide new ideas for the development of new therapeutic measures to target ASD-related behavioral symptoms (biovalleybioon.com) References: Casper C Hoogenraad, Lorena Riol-Blanco.
Interleukin-17: A Social Cytokine Cell
, 30 April 2020, Pages 517-519 doi: 10.1016/j.cell.2020.03.060