IL-27 suppresses Th2 cell development and Th2 cytokines production from polarized Th2 cells: a novel therapeutic way for Th2-mediated allergic inflammation.
IL-27 up-regulates Th1 but down-regulates Th2 responses. However, its molecular mechanism and regulatory effects on polarized Th2 cells remain unclear. In this study, we have revealed that IL-27 inhibits Th2 cell development as well as Th2 cytokines production from already polarized Th2 cells by down-regulation of GATA-3 and up-regulation of T-bet expression simultaneously. In vivo daily IL-27 treatment for 1 wk after Leishmania major infection protects BALB/c mice from footpad swelling by diminishing parasite burden via reciprocal regulation of Th1 and Th2 responses. Furthermore, IL-27 stimulation causes marked reduction in the capacity of host mouse to mount a Th2 response against Strongyloides venezuelensis infection. Thus, IL-27-treated mice failed to develop intestinal mastocytosis after S. venezuelensis infection and exhibited a marked delay in parasite expulsion. Finally, intranasal administration of IL-27 inhibits OVA-induced airway hyperresponsiveness and inflammation in OVA-sensitized animals. Thus, IL-27 could provide us with a novel therapeutic way for treating Th2-associated diseases such as bronchial asthma.
Yoshimoto
Tomohiro
T
Department of Immunology and Medical Zoology, Hyogo College of Medicine, Hyogo, Japan. tomo@hyo-med.ac.jp
Yoshimoto
Takayuki
T
Yasuda
Koubun
K
Mizuguchi
Junichiro
J
Nakanishi
Kenji
K
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D005260:Female; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D020381:Interleukin-17 / Q000276:immunology*; D007896:Leishmaniasis / Q000469:parasitology / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008822:Mice, Transgenic; D018418:Th2 Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D016207:Cytokines; D020381:Interleukin-17