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Calcineurin

A calcium and calmodulin dependent serine/threonine protein phosphatase.

It activates the T cells of the immune system and can be blocked by inhibiting drugs.

It activates nuclear factor of activated T cell cytoplasmic, a transcription factor, by dephosphorylating it.

The activated nuclear factor of activated T cytoplasmic is then translocated into the nucleus, where it upregulates the expression of interleukin 2 (IL-2).

Interleukin 2 in turn, stimulates the growth and differentiation of the T cell response.

Calcineurin is the target of a class of drugs called calcineurin inhibitors, which include cyclosporine, voclosporin, pimecrolimus and tacrolimus.

Antigen-presenting cells interacts with a T cell receptor on T cells, resulting in an increase in the cytoplasmic level of calcium, which activates calcineurin by binding a regulatory subunit and activating calmodulin binding.

Calcineurin induces transcription factors important in the transcription of IL-2 genes.

IL-2 activates T-helper lymphocytes and induces the production of other cytokines.

IL-2 governs the action of cytotoxic lymphocytes.

The amount of IL-2 being produced by the T-helper cells is believed to influence the extent of the immune response significantly.

Calcineurin inhibitors are prescribed for adult rheumatoid arthritis (RA) as a single drug or in combination with methotrexate.

Calcineurin inhibitors also used for psoriatic arthritis, psoriasis, acute ocular Behçet’s disease, juvenile idiopathic arthritis, adult and juvenile polymyositis and dermatomyositis, adult and juvenile systemic lupus erythematosus, adult lupus membranous nephritis, systemic sclerosis, aplastic anemia, steroid-resistant nephrotic syndrome, atopic dermatitis, severe corticosteroid-dependent asthma, severe ulcerative colitis, pemphigus vulgaris, myasthenia gravis, and dry eye disease, with or without Sjögren’s syndrome, administered as ophthalmic emulsion.

Calcineurin is linked to several brain chemical receptors including glutamate, dopamine and GABA.

It may improve the function of diabetics’ pancreatic beta cells.

Tacrolimus contributes to the frequent development of new diabetes following renal transplantation.

Calcineurin signaling is required for perinatal lung maturation and function.

Calcineurin inhibitors are used to suppress the immune system in organ allotransplant recipients to prevent rejection of the transplanted tissue.

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