China currently has a population about 50 million that suffer from autoimmune disorders, with an estimated market size of associated therapeutics over 10 billion yuan. Among, some conditions are common, such as rheumatoid arthritis, lupus, membranous nephritis, inflammatory bowel diseases, psoriasis, atopic dermatitis, allergic asthma etc, some manifestations are rarer, such as anti-glomerular basement membrane disease, myelitis, type I diabetes.  These patients are seen in all specialties of in-patient and out-patient clinics.  GVHD patients after transplantation are seen in surgery and hematology clinics.

For now, long term autoimmune patients rely on immune suppression drugs and steroids, with significant side effects in prolonged use. While biologics, such as anti-TNF-α, IL-17, IL-23 antibodies are in clinics now, these treatments have a relatively narrow suitable indications, and drug resistance after long term use is inevitable.  In addition, some autoimmune patients are refractory to biologics. With increased use, the number of this population accumulates.  On the other hand, some clinical hard-to-treat auto-immunities, such as anti-glomerular basement membrane disease, myelitis, type I diabetes, as well as multiple sclerosis in central nerve system are still facing very limited options. Therefore, there are great needs to develop new innovative therapeutics to serve those patients.

Cell therapies, particularly those based autologous regulatory T cells, are a definitive next step and an unstoppable trend. The reasons are as follows. 
1.Treg binds to antigen presenting cells (DCs), and blocks antigen presentation, and thus stops T cell immune reaction at the very beginning. The technique is therefore more efficient than current methods. 
2.Treg are different from small molecules or biologics, they show in vivo self-adaptation. Other drug molecules enter the blood circulation and often lack organ targeting mechanism; Treg move towards the site of inflammation, per their own design. Treg therapy is thus both efficacious and rational, which is the central strength of cell therapy in contrast to traditional chemical medicines and biologics. 
3.Hard-to-treat autoimmunities urgently call for new methods of intervention. This clinical demand often moves Treg cell therapy to the center of spotlight.  This is evidenced by large capital infusion into new international Treg biotech startups.
Treg are a subpopultion of CD4+ T cells, making up 5-10% of the pool.  Developmentally, there are two groups. 1. Thymic Treg; they are coming from the thymus carrying T cell receptors with relatively strong activities towards self antigens. 2. Induced Treg: they are produced in the periphery, rising as a result of conventional T cells interacting with suppressive DCs and inhibitory cytokines.
Important surface markers: CD4, CD25 (IL2Ra), intracellular marker: FoxP3 (main transcriptional factor)
Treg cell therapy will change the pharmaceutical landscape of ant-autoimmune drugs.
Immune activation is initiated by antigen presentation
Treg block antigen presentation at the very beginning (high efficacy immune suppression)
1.Treg preparation and infusion.  As Treg numbers are small, their sources are limited.  They are also difficult to expand in vitro, therefore it remains a challenge to obtain quantitatively sufficient, stable Treg. This is the reason why while Treg therapy has demonstrated in clinics good safety profile and host tolerance, the therapeutic outcomes are not yet satisfactory. Even the latest Car-Treg/TCR-Treg which use specific receptors to enhance targeting efficacy/reduce infusion doses, they still cannot overcome the issue of Treg expansion and address the stability of these cells after administration.  2.The number of Treg in the host is controlled by inflammatory milieu and homing effects.  It is an ongoing effort to drive the production of Treg via existing in vivo mechanisms, and it also remains elusive how to drive those newly generated cells to their intended locations.  Therefore, by increasing in vivo production of Tregs and their homing capacity, it is possible to increase their capacity of immune suppression.
Number of autoimmune patients and disease categories:
Current interventions:
The opportunities of cell therapy in autoimmune disease treatments:
Current road blockers in Treg cell therapy:
Ryr2-Calpain pathway determines the adhesive property of Treg
J Exp Med. 2017. 
J Clin Invest 2023.
Migratory pathways of dendritic cells determines the local Treg generation and their homing ability
Immunity. 2016.
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