T-cell-specific deletion of gp130 renders the highly susceptible IL-10-deficient mouse resistant to intestinal nematode infection.
Gp130 is the common receptor of the IL-6 family of cytokines and is involved in many biological processes, including acute phase response, inflammation and immune reactions. To investigate the role of gp130 under inflammatory conditions, T-cell-specific conditional gp130 mice were first bred to the IL-10-deficient background and were then infected with the gastrointestinal nematode Trichuris muris. While IL-10(-/-) mice were highly susceptible to T. muris, developed a mixed Th1/Th17 response and displayed severe inflammation of the caecum, infection of mice with an additional T-cell-specific deletion of gp130 signalling completely reversed the phenotype. These mice showed an accelerated worm expulsion that was associated with the rapid generation of a strong Th2 immune response and a significant increase in Foxp3-expressing Treg. Therefore, gp130 signalling in T cells regulates a switch between proinflammatory and pathogenic Th1/Th17 cells and regulatory Th2/Treg in vivo. Taken together, the data demonstrate that gp130 signalling in T cells is a positive regulator of inflammatory processes, favouring the Th1/Th17 axis.
Fasnacht
Nicolas
N
Department of Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Greweling
Marina C
MC
Bollati-Fogolín
Mariela
M
Schippers
Angela
A
Müller
Werner
W
D000818:Animals; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006790:Host-Parasite Interactions; D007113:Immunity, Innate / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism; D007411:Intestinal Diseases, Parasitic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014235:Trichinellosis / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D014258:Trichuris / Q000502:physiology
D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D016753:Interleukin-10; D050822:Cytokine Receptor gp130