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Delivery of IL-35 by Lactococcus lactis Ameliorates Collagen-Induced Arthritis in Mice
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Delivery of IL-35 by Lactococcus lactis Ameliorates Collagen-Induced Arthritis in Mice
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Journal Article
Delivery of IL-35 by Lactococcus lactis Ameliorates Collagen-Induced Arthritis in Mice
2018
Overview
IL-35, a relatively newly discovered cytokine belonging to the larger IL-12 family, shows unique anti-inflammatory properties, believed to be associated with dedicated receptors and signaling pathways. IL-35 plays a pivotal role in the development and the function of both regulatory B (Bregs) and T cells (Tregs). In order to further its therapeutic potential, a dairy
strain was engineered to express murine IL-35 (LL-IL35), and this recombinant strain was applied to suppress collagen-induced arthritis (CIA). Oral administration of LL-IL35 effectively reduced the incidence and disease severity of CIA. When administered therapeutically, LL-IL35 abruptly halted CIA progression with no increase in disease severity by reducing neutrophil influx into the joints. LL-IL35 treatment reduced IFN-γ and IL-17 3.7- and 8.5-fold, respectively, and increased IL-10 production compared to diseased mice. Foxp3
and Foxp3
CD39
CD4
T cells were previously shown to be the Tregs responsible for conferring protection against CIA. Inquiry into their induction revealed that both CCR6
and CCR6
Foxp3
CD39
CD4
T cells act as the source of the IL-10 induced by LL-IL35. Thus, this study demonstrates the feasibility and benefits of engineered probiotics for treating autoimmune diseases.
Publisher
Frontiers Media SA,Frontiers Media S.A
Subject
/ Arthritis, Experimental - immunology
/ Arthritis, Experimental - pathology
/ Arthritis, Experimental - therapy
/ B-Lymphocytes, Regulatory - immunology
/ B-Lymphocytes, Regulatory - pathology
/ Collagen
/ Erythema
/ IL-10
/ IL-35
/ Lactococcus lactis - genetics
/ Lactococcus lactis - immunology
/ Male
/ Mice
/ T-Lymphocytes, Regulatory - immunology
