Kinin receptors: Key regulators of autoimmunity

The central function of the immune system is to protect the host from environmental agents such as microbes or chemicals, thereby preserving the integrity of the body, and preventing the onset of illness and infection. Moreover, the immune system is constantly challenged to discriminate self vs. non-self and mediate the correct response, a phenomenon called self-tolerance. The failure of mechanisms responsible for self-tolerance and induction of an immune response against components of the self, induces autoimmunity and culminates however, in several autoimmune diseases. The precise etiology of autoimmune diseases is not known, although the classic sign of an autoimmune disease is inflammation. In this context, kinins are a family of peptides involved in different physiological and pathological states, comprising inflammatory, vascular and pain processes, and are highly relevant as well as to a variety of diseases including hypertension, kidney diseases, Alzheimer's disease, cancer, obesity, epilepsy and traumatic injuries. These kinin effects are mediated by two related G-protein-coupled receptors named the bradykinin receptors (BKRs), B1 and B2. The kallikrein-kinin system (KKS) and their receptors appear to be involved in both the development and progression of autoimmune diseases, suggesting that modulators of BKRs, administered in monotherapy or in combination with existing therapies, may represent a potential new venue for an effective autoimmune disease treatment. This review article highlights historical and recent progress in understanding the role of BKRs as potential therapeutics for a number of autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, type I diabetes mellitus, inflammatory bowel diseases, and others.