Table 1 GPCRs and their role in autoimmune diseases
GPCRs | Modulators | Effect in autoimmune diseases | Effect in B cell development | References |
|---|---|---|---|---|
S1PR1 | Fingolimod, Siponimod, Ozanimod, Ponesimod, Cenerimod | Fingolimod is the first approval S1PR modulator for the treatment of relapsing MS Ponesimod significantly reduced the psoriasis area and PASI scores in patients Cenerimod is in a Phase II clinical trial for the treatment of SLE | S1PR1 modulators diminish the influx of auto-reactive B cells into the periphery blood, consequently lessening the inflammatory response | [50] [49] |
S1PR3 | Antagonist: TY52156 | S1PR3 was significantly up-regulated in synovium of RA patients | S1P is involved in RA patients' B cell anti-apoptosis | |
CXCR3 | AMG487 Antagonists of WT CXCL11: CXCL11[3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79] and CXCL11[4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79] | Synthetic antagonists of CXCR3 helped alleviate CNS, RA inflammation and reduce the level of antibody in the serum of lupus mice | the expression of CXCR3 on their surface is up-regulated in the patients with NMOSD, IBD and MS CXCR3 level decreased on memory B cells in patients with long-standing type 1 diabetes GC B cells and PC decrease in lupus mice with CXCR3 knockout | [61] |
CXCR4 | Antagonists: CTCE-9908, AMD3100 | CXCR4 antagonist may be used for the treatment of lupus nephritis and bullous pemphigoid | CXCR4 expression was up-regulated in B cells in the lupus mouse model CXCR4-CXCL12 axis extends the lifespan of auto-reactive GC B cells and plasma cells CXCR4+ B cells were enriched in BP lesions and secreted antibodies | [77] [80] |
CXCR5 | / | promote B-cell activation and organization of TLT in autoimmune diseases | Attract B cells to immigrate to inflamed tissues | |
CCR7 | Anti-human CCR7 antibody 8H3-16A12 | Its ligand increased in autoimmune gastritis, RA and AITD | CCR7+ B cell increased in AITD | |
EBI2 | type I interferon down-regulated EBI2 in peripheral B cell subsets Antagonist: NIBR189 | EBI2 is associated with susceptibility of T1D and SLE | EBI2 expression in circulating CD27−IgD+ B cells has been found to help distinguish active SLE patients | [112] |
P2RY8 | / | SLE patients with low P2RY8 expression increased the incidence of nephritis | P2RY8 restrained the development of plasma cells and promote B-cell tolerance. low in P2RY8 led to an increase in ABCs in SLE | [15] |
G2A | Agonist: 8-gingerol, NOX-6–18 | G2A deficiency cause an autoimmune syndrome in aging mice that is similar to human SLE | In G2A−/− mice, auto-reactive B cells activated | |
CB2 | Agonist: WIN55,212–2, CP55,940 Antagonist: SR144528 | CB2 contributes to the protection against MS and IBD | CB2 enhances the expression of IgE by B cells | |
Gpr174 | / | the variants in GPR174 were a risk factor for Graves’ disease and Hashimoto thyroiditis | deregulate the production and ability of autoimmune B cell in males |