Immunosuppressive Exosomes: A New Approach for Treating Arthritis

Table 1

Immunosuppressive exosomes for the treatment of arthritis.

Exosome source	Cell modification/treatment	Model	Application and effect	Reference
BMDC	BMDCs transduced with adenoviral IL-10 or treated with rmIL-10	Mouse	Footpad injection suppressed DTH response; systemic delivery (i.v.) ameliorated CIA progression. The effect requires exosome integrity and MHC class II and B7-1/2 molecules.	[36, 39]
BMDC	BMDCs transduced with adenoviral IL-4 or retroviral IL-4	Mouse	Systemic injection (i.v.) reduced the incidence and severity of established CIA; local injection suppressed DTH response. Exosomes interacted with DCs and macrophages in spleen and liver and were able to modify the function of endogenous APCs and T cells.	[40]
BMDC	BMDCs transduced with adenoviral FasL	Mouse	Local administration suppressed DTH response. The effect was dependent on Fas-FasL interaction and MHC class II molecules. Systemic injection was also effective in treating established CIA.	[42]
BMDC	BMDCs transduced with adenoviral IDO or CTLA4-Ig	Mouse	DC/IDO exosomes were anti-inflammatory in both DTH and CIA models. DC/CTLA4-Ig exosomes reduced DTH response. The effect was dependent on the IDO activity in DCs and partially dependent on B7-1/2 molecules.	[47]
Blood plasma	Exosomes were isolated from the plasma of antigen-immunized mice	Mouse	Local administration of plasma-derived exosomes suppressed DTH response in an antigen-specific manner. The effect was dependent on MHC class II+ exosomes.	[37]
Serum	Exosomes were isolated from physicochemically conditioned autologous patient serum	Human clinical trial	ACS exosomes exhibited anti-inflammatory properties. Local injection of these exosomes was safe and beneficial to RA patients that do not respond to conventional therapy. Reduced joint pain and decreased blood inflammatory markers were observed.	[58–60]