Monocarboxylate transporter MCT1 is a target for immunosuppression.
Nat Chem Biol
; 1(7): 371-6, 2005 Dec.
Article
de En
| MEDLINE
| ID: mdl-16370372
ABSTRACT
Current immunosuppressive therapies act on T lymphocytes by modulation of cytokine production, modulation of signaling pathways or by inhibition of the enzymes of nucleotide biosynthesis. We have identified a previously unknown series of immunomodulatory compounds that potently inhibit human and rat T lymphocyte proliferation in vitro and in vivo in immune-mediated animal models of disease, acting by a novel mechanism. Here we identify the target of these compounds, the monocarboxylate transporter MCT1 (SLC16A1), using a strategy of photoaffinity labeling and proteomic characterization. We show that inhibition of MCT1 during T lymphocyte activation results in selective and profound inhibition of the extremely rapid phase of T cell division essential for an effective immune response. MCT1 activity, however, is not required for many stages of lymphocyte activation, such as cytokine production, or for most normal physiological functions. By pursuing a chemistry-led target identification strategy, we have discovered that MCT1 is a previously unknown target for immunosuppressive therapy and have uncovered an unsuspected role for MCT1 in immune biology.
Recherche sur Google
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Transporteurs d'acides monocarboxyliques
/
Symporteurs
/
Immunosuppresseurs
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Humans
Langue:
En
Journal:
Nat Chem Biol
Sujet du journal:
BIOLOGIA
/
QUIMICA
Année:
2005
Type de document:
Article
Pays d'affiliation:
Royaume-Uni