Cytokines, small molecules, neutralizing antibodies, cell epitopes
|
IL-4/rIL-4 injected subcutaneously
|
Mouse model
|
Increasing Th2 cells and promoting polarization of microglia to the healing M2 phenotype
|
Exerting the function of IL-4
|
Zhao et al. [124]
|
IL-15/IL-15 neutralizing antibody injected subcutaneously
|
Mouse model
|
Decreasing NK, CD8+ T and CD4+ T cells infiltrating the brain
|
Exerting the function of IL-15
|
Lee et al. [126]
|
IL-21/IL-21 receptor Fc protein injected intraperitoneally
|
Mouse model
|
Blocking T cell-derived IL-21 to reduce CD4+ and CD8+ cells infiltrating the brain and attenuate neuronal autography
|
Exerting the function of IL-21
|
Clarkson et al. [127]
|
IL-33/IL-33 injected intraperitoneally
|
Male mouse model
|
Suppressing Th1 cell response as well as improving Treg cell response
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Downregulating the expression of the transcription factor T-bet and upregulating the expression of GATA-3 and Foxp3
|
Xiao et al. [128]
|
PD-1/humanized anti-PD-L1 antibody
|
Mouse model/clinical trial
|
Increasing the appearance of CD8+ regulatory T cells in the lesioned brain and decreasing CNS infiltrating immune cells
|
Unclear
|
Bodhankar et al. [129], Zhang et al.
|
DHA/DHA injected intraperitoneally
|
Mouse model
|
Attenuating the infiltration of T cells into injured brain tissue and promoting polarization of microglia to the healing M2 phenotype
|
Reducing the production of CCL3, CCL17, CXCL10 and CXCL12 to decrease the quantity of T cells
|
Cai et al. [130]
|
GSF/GSF injected intraperitoneally
|
Rat model
|
Attenuating the recruitment of T cell in post-stroke injured brain
|
Reducing blood-brain barrier disruption
|
Dietel et al. [131]
|
CXCL14/2-methoxyestradiol injected intraperitoneally
|
Rat model
|
Inducing Treg differentiation
|
Promoting accumulation of iDC to secrete IL-2 to induce Treg differentiation
|
Lee et al. [132]
|
ACC1/(caloric restriction)
|
Mouse model
|
Balancing peripheral regulatory T cells/T helper 17 (Th17) cells
|
Inhibiting the ACC1 enzyme
|
Wang et al. [133]
|
CD28/CD28SA injected intraperitoneally
|
Mouse model
|
Expanding and amplifying Treg cells that produce IL-10
|
Boosting the production of IL-10
|
Na et al. [134]
|
TLR/The antibodies of TLR2, TLR4 and TLR8
|
Vitro study
|
Reducing the activation of T cells
|
Unclear
|
Tang et al. [135]
|
RTLs/RTL551, RTL100 ] injected subcutaneously
|
Male DR2-Tg mice
|
Inhibiting the activation or infiltration of CD3+ T cells and other proinflammatory cells
|
Modulating T cell functional properties and blocking immune cells infiltrating the brain
|
Zhu et al. [136]
|
Glycyrrhizin (Gly)/injected intraperitoneally
|
Mouse/rat model
|
Inhibiting the activation of CD8+ T and CD4+ T cells
|
Inhibiting HMGB1 release, which promoted T cell proliferation
|
Xiong et al. [137]
|
Exogenous vitamin D3/injected intraperitoneal injection
|
Mouse model
|
Reducing Th17/γδ T cell response and increasing Treg cell response
|
Reducing the expression of proinflammatory mediators IL-6, IL-1β, IL-23a, TGF-β and NADPH oxidase-2 and expression of the transcription factor, ROR-γ
|
Evans et al. [138]
|
Cells
|
Intravenous cellular/injected intravenously (MAPCs)
|
Animal model/clinical trial
|
Reducing proinflammatory cells including CD3+ T, CD4+ T and CD8+ T cells and promoting Tregs
|
Relating to multiple mechanisms of action
|
Mays et al. [139]
|
Treg
|
Treg/antibiotic-induced intestinal flora alteration
|
Mouse model
|
Increasing regulatory T cells and reducing IL-17+ γδ T cells
|
Altering dendritic cell activity to induce Treg cell differentiation more effectively
|
Benakis et al. [140]
|
Treg/adoptively transferred Treg
|
Mouse model
|
Increasing the number and/or function of Treg
|
Unclear
|
Xia et al. [141]
|
Brain antigen/intranasal instillation
|
MBP
|
Male rat model
|
Suppressing Th1 response and increasing the probability of Tr1, Th3 or other Tregs responses
|
Inducing mucosal tolerance
|
Gee et al. [142]
|
E-selection
|
SHR-SP rat model
|
Chen et al. [143]
|
MOG
|
Female rat model
|
Frenkel et al. [144]
|
Drugs
|
Levodopa/benserazide/injected intraperitoneally
|
Rat model
|
Reducing CD8+ cells infiltrating the injured brain
|
Reducing the expression of ICAM-1 on endothelial cells in the brain to inhibit adhesion of cytotoxic T cells infiltrating the brain parenchyma
|
Kuric et al. [145]
|
Natalizumab/injected intravenously
|
Clinical trial
|
Blocking T cell infiltration into the brain
|
Blockade of the α4-β1 integrin on leukocytes
|
Veltkamp et al. [146], Fu et al. [147]
|
Fingolimod/orally
|
Clinical trial
|
Reducing peripheral lymphocytes
|
An oral S1P receptor modulator that sequesters lymphocytes to lymph nodes
|
Veltkamp et al. [131], Fu et al. [147]
|