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4‐1BB triggers IL‐13 production from T cells to limit the polarized, Th1‐mediated inflammation
Author(s) -
Shin Su M.,
Kim Young H.,
Choi Beom K.,
Kwon Patrick M.,
Lee HyeonWoo,
Kwon Byoung S.
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1006619
Subject(s) - biology , cytotoxic t cell , t cell , immune system , cd137 , microbiology and biotechnology , cd8 , zap70 , inflammation , cd28 , interleukin 21 , stimulation , immunology , endocrinology , in vitro , biochemistry
4‐1BB (CD137) triggering typically induces Th1 response by increasing IFN‐γ from T cells upon TCR ligation. We found recently that 4‐1BB costimulation increased the expression of IL‐13 from CD4 + T cells, as well as CD8 + T cells. The enhanced IL‐13 expression by agonistic anti‐4‐1BB treatment was mediated via MAPK1/2, PI‐3K, JNK, mammalian target of rapamycin, NF‐AT, and NF‐κB signaling pathways. The signaling for IL‐13 induction was similar to that of IFN‐γ production by anti‐4‐1BB treatment in T cells. When the anti‐4‐1BB‐mediated IL‐13 expression was tested in an in vivo viral infection model such as HSV‐1 and vesicular stomatitis virus, 4‐1BB stimulation enhanced IL‐13 expression of CD4 + T, rather than CD8 + T cells. Although IL‐13 was enhanced by anti‐4‐1BB treatment, the increased IL‐13 did not significantly alter the anti‐4‐1BB‐induced Th1 polarization of T cells—increase of T‐bet and decrease of GATA‐3. Nevertheless, anti‐4‐1BB treatment polarized T cells excessively in the absence of IL‐13 and even became detrimental to the mice by causing liver inflammation. Therefore, we concluded that IL‐13 was coinduced following 4‐1BB triggering to maintain the Th1/2 balance of immune response.