Persistence of effector memory Th1 cells is regulated by Hopx.
Th1 cells are prominent in inflamed tissue, survive conventional immunosuppression, and are believed to play a pivotal role in driving chronic inflammation. Here, we identify homeobox only protein (Hopx) as a critical and selective regulator of the survival of Th1 effector/memory cells, both in vitro and in vivo. Expression of Hopx is induced by T-bet and increases upon repeated antigenic restimulation of Th1 cells. Accordingly, the expression of Hopx is low in peripheral, naïve Th cells, but highly up-regulated in terminally differentiated effector/memory Th1 cells of healthy human donors. In murine Th1 cells, Hopx regulates the expression of genes involved in regulation of apoptosis and survival and makes them refractory to Fas-induced apoptosis. In vivo, adoptively transferred Hopx-deficient murine Th1 cells do not persist. Consequently, they cannot induce chronic inflammation in murine models of transfer-induced colitis and arthritis, demonstrating a key role of Hopx for Th1-mediated immunopathology.
German Rheumatism Research Center Berlin, Berlin, Germany.
Inka
I
Albrecht
Uwe
U
Niesner
Marko
M
Janke
Astrid
A
Menning
Christoph
C
Loddenkemper
Anja A
AA
Kühl
Inga
I
Lepenies
Maria H
MH
Lexberg
Kerstin
K
Westendorf
Kristyna
K
Hradilkova
Joachim
J
Grün
Alf
A
Hamann
Jonathan A
JA
Epstein
Hyun-Dong
HD
Chang
Koji
K
Tokoyoda
Andreas
A
Radbruch
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001168:Arthritis / Q000276:immunology / Q000473:pathology; D002470:Cell Survival / Q000276:immunology; D003092:Colitis / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000276:immunology*; D018398:Homeodomain Proteins / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology*; D025521:Tumor Suppressor Proteins / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology
C491901:FAS protein, human; C491899:Fas protein, mouse; C476884:HOPX protein, human; C473013:Hod protein, mouse; D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; D019014:fas Receptor