Anti-IL22 monoclonal antibody, clone 253007

The role of tumour necrosis factor-alpha (TNF-) is not fully understood in human leishmaniasis. We analysed the alterations in the levels of TNF-, soluble TNF receptor type 1 (sTNFR I), IL-17 and IL-22 productions in active and healed leishmaniases. Blood samples were collected from volunteers with active cutaneous leishmaniasis (ACL), the same subjects after lesion healing (healed CL=HCL), volunteers with active visceral leishmaniasis (AVL), healed VL (HVL) and healthy controls. Levels of cytokines were titrated on Leishmania Ag-stimulated PBMC culture. The mean level of TNF- production from stimulated cells was significantly higher in ACL than controls (P<0001) and significantly reduced after treatment in HCL volunteers (P<005). The mean level of sTNFR I production was significantly higher in ACL than controls (P<0001) and significantly reduced after treatment in HCL volunteers (P<005). The mean level of IL-22 production in AVL was significantly higher than controls (P<005) and was significantly lower in HVL compared with AVL (P<0001) and controls (P<005). The levels of TNF- (P=00025) and sTNFR I (P<001) productions from PBMCs showed significant decreasing trend after treatment in each CL volunteer. Reduction in TNF- is associated with clinical response to treatment and healing of CL lesions due to L.major.

High-dose chemotherapy and/or radiation given before an allogeneic hematopoietic cell transplantation severely damage thymic epithelial cells (TECs), resulting in poor post-transplant immune recovery. IL-22 mediates recovery of TECs via a proregenerative effect, but the precise mechanism by which this occurs is unknown. In this study, we found IL-22 improved thymus recovery after damage from irradiation in association with increased number of TECs. This effect was blocked by ruxolitinib, a JAK1/JAK2 inhibitor. IL-22 increased the number of TECs via a Stat3-dependent signaling in the mTEC1 murine thymic epithelial cell line. This, in turn, upregulated transcription of myeloid cell leukemia sequence 1 (Mcl1), resulting in increased number of TECs. Similar effects were seen in irradiated mice given IL-22. Defects in IL-22 resulted in delayed thymus recovery in irradiated mice and had an impact on levels of thymus function-related genes such as Foxn1, Aire, and Kgf. In mice, post-transplant use of IL22 improved repair of TECs, increased the numbers of thymus T cells, increased the intrathymic levels of Aire, and increased the proportion of natural regulatory T cells, resulting in decreased severity of chronic graft-versus-host disease (GVHD). Our data highlight the critical role of the IL-22/Stat3/Mcl-1 pathway in the regeneration of TECs after damage from irradiation in mice and highlight circumstances where normalizing thymus T cell function with IL-22 decreases GVHD after allotransplants. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.