Background and Aims

Where there are helminthes , autoimmunity is rare. The aim of the helminthes is to protect themselves via immunomodulation of the host immune network. We have constructed a bi-functional compound consists of phosporylcholine-tuftsin (TPC). The aim was to prove its immunomodulatory function in murine models of autoimmune diseases and in ex-vivo human models.

Methods

We introduced TPC to murine models of autoimmune diseases such as lupus NZBxW/F1 mice, collagen-induced-arthritis (CIA), dextransulfatsodiumsalt-(DSS)-induced-colitis, experimental-autoimmune-encephalomyelitis (EAE) and showed its cytokines production and Tregulatory profile. Ex-vivo using human peripheral-mononuclear-cells (PBMCs) or biopsies from patients with giant-cell-arteritis (GCA) and lupus were analyzed for cytokines production.

Results

TPC attenuated the clinical score of murine autoimmune models of lupus CIA, DSS-induced-colitis and EAE . TPC decreased significantly the secretion of inflammatory cytokines (TNFa, IL-1b, IL-6, IFNg) and enhanced production of anti-inflammatory IL-10, expanded T and B regulatory cells. Likewise, TPC had an equal effect as methylprednisolone in a mouse model of lupus, inhibiting disease development in established lupus. Furthermore, The immunomodulatory activity of TPC was proven also ex-vivo in lupus and GCA reducing the inflammatory cytokines production by patients PBMCs and in biopsies from GCA.

The bi-functional immunomodulatory activity of TPC was attributed to: a) The PC part which inhibited significantly TLR4 expression by HEKTM-mTLR4 cells, through NFkB expression; b) TPC shifts macrophage cells from pro-inflammatory macrophages M1 to anti-inflammatory M2-secreting IL-10 and induce Tregs through the neuropilin-1.

Conclusions

Our data propose the potential novel therapy to treat autoimmune condition.Our data propose the potential novel therapy to treat autoimmune condition.