TACI

TACI is the acronym for " transmembrane activator and calcium modulating cyclophilin ligand interactor ".TACI, also known as tumor necrosis factor receptor superfamily member 13B (TNFRSF13B), is a transmembrane protein of the TNF receptor superfamily that in humans is encoded by the TNFRSF13B gene. The coding gene is located in the so-called Smith-Magenis syndrome region on chromosome 17.

TACI is predominantly found on the surface of B cells. ACI recognizes three ligands: APRIL, BAFF and CAML. TACI is a regulator in the immune response. Via BAFF and APRIL, TACI causes the activation of various transcription factors. These include NFAT, AP-1 and NF-kappa-B, which modulate various cellular activities. Furthermore, TACI inhibits B cell expansion and promotes plasma cell differentiation and survival.

The mechanisms underlying these effects are likely associated with altered expression of some key molecules such as B-lymphocyte-induced maturation protein-1(Blimp1) and inducible T-cell costimulatory ligand (ICOSL) in B cells and/or plasma cells.

The cytokine was originally discovered because of its ability to interact with calcium modulator and cyclophilin ligand (CAML) (Zhang Y et al. (2015).

TACI mutations are associated with immunodeficiency in humans, as a significant proportion of CVID patients have TACI mutations (Karaca NE et al. 2018; Freiberger T et al. 2012). People with this disorder produce abnormally low levels of antibodies needed for protection against infection. In animal experiments, defective TACI can lead to lethal autoimmunity and cause symptoms that resemble SLE (Zhang Y et al. (2015).

TACI is currently targeted against autoimmunity and B-cell malignancies via atacicept, a recombinant fusion protein that binds the TACI ligands BAFF and APRIL.

1. Freiberger T et al. (2012) Sequence variants of the TNFRSF13B gene in Czech CVID and IgAD patients in the context of other populations. Hum Immunol 73:1147-1154.
2. Karaca NE et al. (2018) TNFRSF13B/TACI alterations in Turkish patients with common variable immunodeficiency and IgA deficiency. Avicenna J Med Biotechnol10:192-195.
3. Schäffer AA et al. (2006) Analysis of families with common variable immunodeficiency (CVID) and IgA deficiency suggests linkage of CVID to chromosome 16q. Hum Genet 118:725-729.
4. Speletas M et al (2011) TNFRSF13B/TACI alterations in Greek patients with antibody deficiencies. J Clin Immunol 31:550-559.
5. Zhang Y et al (2015) Effect of TACI signaling on humoral immunity and autoimmune diseases. J Immunol Res 2015:247426.