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Brain control of humoral immune responses amenable to behavioural modulation 
Xu Zhang, et.al
Nature, 2020 It has been speculated that brain activities might directly control adaptive immune responses in lymphoid organs, although there is little evidence for this. In this paper, the authors found that surgical splenic denervation affected SPPC formation in a T cell dependent manner after immunization by NP-KLH. As the splenic nerve releases norepinephrine, they demonstrated that developing SPPC were responded to acetylcholine directly by intravenous infusion of norepinephrine or acetylcholine during immunization, and by transduction of B cells with membrane-anchored acetylcholinesterase. Meanwhile, they obtained Chrnb9 was the main acetylcholine receptor on B cells by using CRISPER-Cas9 gene editing technique and confirmed this by bone marrow chimaeric mice with immunization. Further, they demonstrated that ChAT-expressing activated T cells serve as a relay between the sympathetic splenic nerve and the acetylcholine-responsive process of SPPC formation. To trace the brain origin of splenic nerve-dependent immuno-stimulatory neural activity, they conducted retrograde tracing by injecting fluorescent protein-expressing recombinant pseudo-rabies virus (PRV) Bartha strain into the spleen and by inhibiting or activating CRHneuronal activity indicated CRH produced by CeA and PVN could be transmitted through splenic nerve to promote SPPC formation. Finally, they investigated that mice received mild stress daily which were subjected to stand on a platform to induce mild stress, could affect SPPC formation after NP-KLHimmunization and also enhanced the antigen-specific antibody response via the CeA/PVN- splenic nerve axis.In summary, their findings demonstrate brain control of adaptive immunity via direct neural connection. Most significantly, they found the bodily behaviours and psychological conditioning are linked to neuron activation in specific brain areas, which have an impact on adaptive immunityHallmarks of T cell aging
Maria Mittelbrunn & GuidoKroemer Nature Immunology, 2021 The aged adaptive immune system is characterized by progressive dysfunction as well as increased autoimmunity. Recent evidence indicates that CD4+ Tcell–intrinsic alterations contribute to chronic inflammation and are sufficient to accelerate an organism-wide aging phenotype, supporting the idea that T cell aging plays a major role in body-wide deterioration. In this Review, the authors propose ten molecular hallmarks to represent common denominators of T cell aging. These hallmarks are grouped into four primary hallmarks (thymic involution, mitochondrial dysfunction, genetic and epigenetic alterations, and loss of proteostasis) and four secondary hallmarks(reduction of the TCR repertoire, naive–memory imbalance, T cell senescence, and lack of effector plasticity), and together they explain the manifestation of the two integrative hallmarks (immunodeficiency and inflammaging). A major challenge now is weighing the relative impact of these hallmarks on T cell aging and understanding their interconnections, with the final goal of defining molecular targets for interventions in the aging process.Senescent T cells acquire additional features of senescence, including low telomerase activity and short telomeres; signs of DNA damage, such as γH2AX foci; apoptosis resistance; and β-galactosidase activity. Moreover, senescent T cells lose the expression of the costimulatory molecules CD27 and CD28 and upregulate the expression of terminal-differentiation markers, such as KLRG1. In sum, with age, senescent T cells with reduced immune but elevated proinflammatory functions accumulate.
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