Butyrophilins

Butyrophilins (BTN family), similarly as the B7 family of regulatory proteins, belongs to the immunoglobulin (Ig) superfamily. Butyrophilins are glycoproteins contain two extracellular immunoglobulin domains, stabilized with disulfide bonds: constant IgC, and variable IgV and a transmembrane region. Butyrophilins are present on lymphocytes, dendritic cells, monocytes, macrophages, neutrophils and eosinophils, and acts as immune system regulators (stimulatory or inhibitory effect). In humans, BTN family includes 7 butyrophilin proteins (BTN1A1, BTN2A1, BTN2A2, BTN2A3, BTN3A1, BTN3A2, BTN3A3), 5 butyrophilin-like proteins (BTNL) (BTNL2, BTNL3, BTNL8, BTNL9, BTNL10) and the SKINT-like factor (SKINTL-selection and upkeep of intraepithelial T-cells), while in mice, 11 proteins of this family have been described: BTN1A1, BTN2A2, BTNL1, BTNL2, BTLN4, BTNL5, BTNL6, BTNL7, BTNL9, BTNL10 and SKINTL, which differ in humans and mice. Butyrophilins have been also demonstrated to play a role in various infections, e.g. tuberculosis or diseases that include sarcoidosis, systemic lupus erythematosus, rheumatoid arthritis, genetic metabolic diseases, ulcerative colitis, cancer and kidney disease. Noteworthy, some BTN/BTNLs are co-inhibitory whereas others are co-stimulatory in the regard of conventional T cell function regulation. For instance, human BTN3A1 (CD277), mouse BTNL2 and murine BTNL1 are considered as co-inhibitory molecules; BTNL8 and BTN3A2 are recognized as co-stimulatory molecules.