Immunophilins

Immunophilins are a family of small intracellular proteins that function as peptidyl-prolyl cis-trans isomerases (PPIases) and often serve as molecular chaperones. By catalyzing isomerization of peptide bonds at proline residues, they influence protein folding, conformation, and trafficking. Immunophilins are classified into three families: cyclophilins, FK506-binding proteins (FKBPs), and parvulins. They are named in part for their ability to bind clinically important immunosuppressive drugs, linking their cellular roles to immune regulation.

Cyclophilins bind cyclosporine A (CsA), while FKBPs bind tacrolimus (FK506) and related compounds. Drug–immunophilin complexes block signaling pathways that are essential for T cell activation: CsA–cyclophilin and FK506–FKBP complexes inhibit calcineurin, reducing cytokine production; rapamycin (sirolimus) forms a complex with FKBP12 that inhibits mTOR, blocking cell growth and proliferation. These interactions underpin the use of these drugs in organ transplantation and autoimmunity.

Physiologically, immunophilins participate in protein folding and quality control, signal transduction, and intracellular trafficking. Specific members have distinctive roles: cyclophilins (e.g., cyclophilin A and B) are widely distributed and implicated in inflammation and host–pathogen interactions; FKBP family members include small cytosolic proteins like FKBP12 and larger, regulatory proteins such as FKBP52 that influence steroid receptor signaling; parvulins, such as Pin1, regulate cell cycle and signaling via proline-directed isomerization.

In clinical and research contexts, immunophilins are studied as drug targets, modulators of immune responses, and factors in viral replication and cancer biology.