Abstract
Th2–eosinophil immune responses are well known for mediating host defence against helminths. Herein we describe a function of Th2–eosinophil responses in counteracting the development of arthritis. In two independent models of arthritis, Nippostrongylus brasiliensis infection leads to Th2 and eosinophil accumulation in the joints associated with robust inhibition of arthritis and protection from bone loss. Mechanistically, this protective effect is dependent on IL-4/IL-13-induced STAT6 pathway. Furthermore, we show that eosinophils play a central role in the modulation of arthritis probably through the increase of anti-inflammatory macrophages into arthritic joints. The presence of these pathways in human disease is confirmed by detection of GATA3-positive cells and eosinophils in the joints of rheumatoid arthritis patients. Taken together, these results demonstrate that eosinophils and helminth-induced activation of the Th2 pathway axis effectively mitigate the course of inflammatory arthritis.
Highlights
Th2–eosinophil immune responses are well known for mediating host defence against helminths
N. brasiliensis inhibited arthritis associated with Th2 cells
To confirm the inhibitory effect of N. brasiliensis-induced Th2 responses on arthritis, we examined a second model of arthritis and challenged 5-week-old human tumour necrosis factor (TNF) transgenic mice with N. brasiliensis
Summary
Th2–eosinophil immune responses are well known for mediating host defence against helminths. We show that eosinophils play a central role in the modulation of arthritis probably through the increase of anti-inflammatory macrophages into arthritic joints The presence of these pathways in human disease is confirmed by detection of GATA3-positive cells and eosinophils in the joints of rheumatoid arthritis patients. Severe infections are rare and adults suffer of mild or asymptomatic disease Helminths such as N. brasiliensis trigger robust Th2 responses in vivo, characterized by increased production of Th2 cytokines such as interleukin (IL)-4 and IL-13, accompanied with activation and expansion of CD4 þ Th2 cells, eosinophilia, goblet and mucosal mast cell hyperplasia[6,7,8,9,10,11]. IL-5producing cells were increased already early and returned to baseline level 6 days after induction of arthritis (Fig. 1i) All together, these data showed a profound Th2 response after N. brasiliensis challenge during the onset of arthritis
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