Table 2 The impact of various immune cell types on CNS diseases.
Disease | Cell type | Characteristic |
|---|---|---|
MS | Myeloid cells | Monocyte entry into the brain and spinal cord is required for progression to severe stages of EAE [156]. |
The neutrophil-to-lymphocyte ratio is positively correlated with patient prognosis [157]. | ||
Lymphocytes | Autoreactive T cells enter the bone marrow through the CXCL12–CXCR4 axis, promoting bone marrow regeneration and disease occurrence, they also promote increased neutrophil and ly6chigh monocyte production through the CCL5–CCR5 axis, promoting disease progression [156]. | |
B cells are significantly enriched in the CSF and brain tissue of MS patients [158]. | ||
Natural killer (NK) cells inhibit T cell proliferation, kill autoreactive T cells, suppress the differentiation of myelin-reactive T helper type 1 (Th1) and type 17 (Th17) cells in the CNS, and secrete neurotrophic factors [159,160,161,162,163,164]. | ||
Lymphocytes | The number of CD8+ T cells significantly increases in cerebral ischemic tissue [165,166,167,168,169]. | |
AD | Myeloid cells | The ability of monocytes to engulf amyloid beta (Aβ) is impaired, and they can release cytotoxic factors that disrupt the BBB [170]. Neutrophils promote AD-like pathology and cognitive decline through LFA-1 integrin [171]. |
Lymphocytes | B cells alleviate Aβ load and cognitive impairment in 5×FAD mice by producing IL-35 [172]. Increased activated CD8+ T cells are found in the CSF and blood of mild AD patients [173]. | |
.PD | Myeloid cells | Impaired phagocytic ability of monocytes and macrophages towards α-synuclein [174, 175]. |
Lymphocytes | CD4+CD8+ T cells can respond to α-synuclein to produce Th1/Th2 cytokines, but the impact of CD4+ T cells that produce IFN-γ is greater than that of CD8+ T cells. CD4+ T cells can promote neuronal degeneration [176]. | |
B cells play a dual role in PD, functioning both to inhibit inflammation by releasing anti-inflammatory factors via regulatory B cells and to promote neuroinflammation by activating T cells and releasing antibodies through pro-inflammatory B cells [38, 118]. | ||
In preclinical mouse models of PD, NK cells have been shown to be scavengers of α-synuclein. Systemic depletion of NK cells exacerbates α-synuclein synaptic nuclear protein pathology, while systematic clearance of α-synuclein can alleviate the pathological changes caused by α-synuclein [177] | ||
Aging | Myeloid cells | Aging is accompanied by an increase in neutrophils. Due to enhanced PI3K signaling within cells, chemotaxis is weakened, and phagocytic bactericidal ability is impaired [178,179,180,181]. |
During aging in mice and humans, the production of classical monocytes expressing MHCII increases [182]. | ||
Lymphocytes | Decreased NK cell numbers in multiple organs of elderly mice [183]. | |
ALS | Myeloid cells | The neutrophil-to-lymphocyte ratio is negatively correlated with the survival time of ALS patients [184]. |
Lymphocytes | A high frequency of CD4+FOXP3- effector T cells in blood and CSF is associated with a low survival rate, while a high frequency of activated regulatory T (Treg) cells in blood and a high ratio between activation and resting states are associated with a better survival rate [185]. | |
Brain injury | Myeloid cells | Sudden adrenergic activation following acute brain injury biases bone marrow HSCs toward the myeloid lineage, resulting in increased production of Ly6Clow patrol monocytes. These monocytes migrate into the injured brain and reduce neuroinflammation [52]. |
Skull bone marrow-derived neutrophils rapidly migrate to brain tissue, releasing NETs and inflammatory factors, exacerbating neuroinflammation [3, 25]. | ||
Major depressive disorder | Myeloid cells | Under long-term chronic stress, the sympathetic nervous system in the bone marrow releases norepinephrine, inhibiting CXCL12 expression and thereby promoting the release of monocytes and neutrophils [186,187,188,189,190,191]. |
Ly6Chigh monocytes and neutrophils release MMP8, which controls the ultrastructure of the extracellular space of neurons, thereby affecting neuronal function [192]. | ||
Lymphocytes | Reduction in CD4+CB+ T cells is associated with an enhanced immune inflammatory response system in major depressive disorder [193]. |
