IL-3 attenuates collagen-induced arthritis by modulating the development of Foxp3+ regulatory T cells.
IL-3, a cytokine secreted by Th cells, functions as a link between the immune and the hematopoietic system. We previously demonstrated the potent inhibitory role of IL-3 on osteoclastogenesis, pathological bone resorption, and inflammatory arthritis. In this study, we investigated the novel role of IL-3 in development of regulatory T (Treg) cells. We found that IL-3 in a dose-dependent manner increases the percentage of Foxp3(+) Treg cells indirectly through secretion of IL-2 by non-Treg cells. These IL-3-expanded Treg cells are competent in suppressing effector T cell proliferation. Interestingly, IL-3 treatment significantly reduces the severity of arthritis and restores the loss of Foxp3(+) Treg cells in thymus, lymph nodes, and spleen in collagen-induced arthritis mice. Most significantly, we show that IL-3 decreases the production of proinflammatory cytokines IL-6, IL-17A, TNF-α, and IL-1 and increases the production of anti-inflammatory cytokines IFN-γ and IL-10 in collagen-induced arthritis mice. Thus, to our knowledge, we provide the first evidence that IL-3 play an important role in modulation of Treg cell development in both in vitro and in vivo conditions, and we suggest its therapeutic potential in the treatment of rheumatoid arthritis and other autoimmune diseases.
National Centre for Cell Science, University of Pune Campus, Pune 411 007, India.
Rupesh K
RK
Srivastava
Geetanjali B
GB
Tomar
Amruta P
AP
Barhanpurkar
Navita
N
Gupta
Satish T
ST
Pote
Gyan C
GC
Mishra
Mohan R
MR
Wani
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation / Q000276:immunology*; D003094:Collagen / Q000008:administration & dosage*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D007377:Interleukin-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007377:Interleukin-3; D011994:Recombinant Proteins; D003094:Collagen