Can we selectively shut off immune responses?

Abstract

Immune system is essential for our survival and healthy for it being able to exert diverse functions including innate immunity and adaptive immune responses. While our immune system has architecture of precise regulation and fine-tuned functionality, their loss of regulations or balances will lead to serious consequences including transplant rejection, autoimmune disease, allergy and cancer. Therefore, the key for effective therapies is how we are able to selectively shut off specific immune response. In about a century, the medical research of how to decrease or sweep out the rejection response toward the transplanted organ is a representative for regulating specific immune responses. Many strategies for weakening undesired immune responses by immunosuppression have made the organ transplantation a reality, saving the lives of many thousands people. However, for prolonging the life time of the transplanted organ and survival of the patient, lifelong medication is indispensable. Unfortunately, lifelong medication cannot clear all rejection responses; what is worse is that it suppresses the normal immune protection, a side effect that is so serious that makes patients suffer and threatens patients of losing their lives caused by infection and cancer. To a large degree, these circumstances are similar with the therapies toward autoimmune disease and allergy, two obstinate immunodeficiency diseases caused by genetic defect and pathogen infection mainly. For finding better therapies, extensive researches have been carried out to elucidate the molecular bases of pathogenesis of autoimmune disease and allergy. Nonetheless, there is still no specific therapy that just targets undesired immune responses and spares normal immune responses. Based on our understandings of self-tolerance that spares self-antigens by clone deletion or clone anergy, studies using bone marrow chimerism and production of regulatory T cells have shown effective induction of immune tolerance toward transplanted antigens in animal models for the treatment of rejection response. In the future, artificial organs and inducible pluripotent stem (iPS) cells may provide better therapies for immune rejection, and genome-editing techniques such as CRISP will be useful for autoimmune disease caused by genetic defect. The best solution in the treatment of these diseases depends on our ability to selectively shut off specific immune responses. Recently, some key immune check points have been found to be critical for cancer's escape of immune surveillance. A first useful medicine called nivolumab, based on anti-PD-1 (Programmed cell death protein 1), has been approved two years ago. Now, even though serious challenges are ahead, we are in an age when we are able to selectively shut off specific immune responses so as to provide better treatments for various diseases.