Human CD4+CD25+ regulatory T cells: proteome analysis identifies galectin-10 as a novel marker essential for their anergy and suppressive function.
CD4(+)CD25(+)Foxp3(+) regulatory T cells (CD25(+) Treg cells) direct the maintenance of immunological self-tolerance by active suppression of autoaggressive T-cell populations. However, the molecules mediating the anergic state and regulatory function of CD25(+) Treg cells are still elusive. Using differential proteomics, we identified galectin-10, a member of the lectin family, as constitutively expressed in human CD25(+) Treg cells, while they are nearly absent in resting and activated CD4(+) T cells. These data were confirmed on the mRNA and protein levels. Single-cell staining and flow cytometry showed a strictly intracellular expression of galectin-10 in CD25(+) Treg cells. Specific inhibition of galectin-10 restored the proliferative capacity of CD25(+) Treg cells and abrogated their suppressive function. Notably, first identified here as expressed in human T lymphocytes, galectin-10 is essential for the functional properties of CD25(+) Treg cells.
Kubach
Jan
J
Department of Dermatology, Johannes Gutenberg-University, Mainz, Germany.
Lutter
Petra
P
Bopp
Tobias
T
Stoll
Sabine
S
Becker
Christian
C
Huter
Eva
E
Richter
Christoph
C
Weingarten
Petra
P
Warger
Tobias
T
Knop
Jürgen
J
Müllner
Stefan
S
Wijdenes
John
J
Schild
Hansjörg
H
Schmitt
Edgar
E
Jonuleit
Helmut
H
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015415:Biomarkers; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000187:drug effects / Q000276:immunology*; D051858:Forkhead Transcription Factors; D037161:Galectins / Q000037:antagonists & inhibitors / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D020543:Proteome / Q000276:immunology*; D017634:Self Tolerance / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D037161:Galectins; D020543:Proteome; C523496:galectin 10, human