Trojan Horse Nanocapsule Enabled In Situ Modulation of the Phenotypic Conversion of Th17 Cells to Treg Cells for the Treatment of Multiple Sclerosis in Mice

Abstract

Th17/Treg imbalance is closely related to the occurrence and development of multiple sclerosis (MS), and the transdifferentiation of Th17 cells into Treg cells may contribute to the resolution of inflammation, presenting a therapeutic strategy for MS. To modulate this phenotypic shift in situ, a “Trojan horse”‐like hybrid system, nanocapsule‐coupled Th17 cells, is reported for MS treatment. Following intravenous injection into MS mice, the hybrid system efficiently transmigrates across the blood–brain barrier and homes to the inflamed MS niche. (Aminooxy)‐acetic acid, a transdifferentiation inducer, is locally released upon the production of ROS and in turn taken up by Th17 cells. It is demonstrated that the Trojan horse hybrid system enables in situ phenotypic transdifferentiation of Th17 cells into anti‐inflammatory Treg cells. This phenotypic conversion leads to a domino‐like immune response that is conducive to MS therapy. Overall, this work highlights a new pathway for accurate modulation of the phenotypes of adoptively transferred cells in situ, from proinflammatory to anti‐inflammatory for MS therapy, and may be broadly applicable for patients suffering from other autoimmune diseases.

Reduced serum IgG galactosylation is associated with increased inflammation during relapses of neuromyelitis optica spectrum disorders

“…While our findings in NMOSD are in line with numerous autoimmune disease studies, they diverge from observations in MS due to several factors. There are several factors could account for this disparity: (a) MS is primarily an autoimmune disorder mediated by the cellular immune system where T cells, such as Th17 (34)(35)(36) and Treg (37)(38)(39), contribute significantly to its pathogenesis, and the minor pro-inflammatory effect of IgG galactosylation may be counteracted. In contrast, the pathological process of NMOSD is more linked to humoral immunity and antibody-producing cells, particularly B lymphocytes, due to the crucial role of anti-AQP4 autoantibodies in triggering the disease.…”

Nanotechnology’s frontier in combatting infectious and inflammatory diseases: prevention and treatment

“… 498 ROS-reactive drug administration platforms have remarkable performance in biomedical fields as their payload is exclusively delivered at inflamed areas marked by high ROS levels. 499 , 500 …”

“…Therefore, employing a “Trojan horse” strategy, Th17 cells could be used as powerful cell carriers for cascade-based medicinal drug trans BBB. 500 In cerebral ischemia, neutrophils travel from the bloodstream and cross the BBB and gather in vast numbers at the region of irritation. The peptide cinnamyl-F-(D)L-F-(D)L-F, which may selectively attach to the formyl peptide receptor (FPR), is employed to modify a nanocomplex interface as the membrane of neutrophils includes FPR.…”

“…It is shown that Th17 cells can phenotypically transdifferentiate in situ into anti-inflammatory Treg cells utilizing the Trojan horse recombinant approach. 500 …”

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“…In addition, Th17 cells are also involved in various autoimmune diseases, and their pathogenic role in inflammatory bowel disease has been well established [ 41 ]. Th17 has also been reported to be a key participant in psoriasis, Rheumatoid arthritis, Crohn's disease, Ulcerative colitis, multiple sclerosis, and Ankylosing spondylitis [ 33 , 42 , 43 ].…”