Dataset Information

The IL-12 Cytokine and Receptor Family in Graft-vs.-Host Disease.

ABSTRACT: Allogeneic hematopoietic cell transplantation (allo-HCT) is performed with curative intent for high- risk blood cancers and bone marrow failure syndromes; yet the development of acute and chronic graft-vs.-host disease (GVHD) remain preeminent causes of death and morbidity. The IL-12 family of cytokines is comprised of IL-12, IL-23, IL-27, IL-35, and IL-39. This family of cytokines is biologically distinct in that they are composed of functional heterodimers, which bind to cognate heterodimeric receptor chains expressed on T cells. Of these, IL-12 and IL-23 share a common ? cytokine subunit, p40, as well as a receptor chain: IL-12R?1. IL-12 and IL-23 have been documented as proinflammatory mediators of GVHD, responsible for T helper 1 (Th1) differentiation and T helper 17 (Th17) stabilization, respectively. The role of IL-27 is less defined, seemingly immune suppressive via IL-10 secretion by Type 1 regulatory (Tr1) cells yet promoting inflammation through impairing CD4+ T regulatory (Treg) development and/or enhancing Th1 differentiation. More recently, IL-35 was described as a potent anti-inflammatory agent produced by regulatory B and T cells. The role of the newest member, IL-39, has been implicated in proinflammatory B cell responses but has not been explored in the context of allo-HCT. This review is directed at discussing the current literature relevant to each IL-12-family cytokine and cognate receptor engagement, as well as the consequential downstream signaling implications, during GVHD pathogenesis. Additionally, we will provide an overview of translational strategies targeting the IL-12 family cytokines, their receptors, and subsequent signal transduction to control GVHD.

SUBMITTER: Bastian D

PROVIDER: S-EPMC6518430 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The IL-12 Cytokine and Receptor Family in Graft-vs.-Host Disease.

Bastian David D Wu Yongxia Y Betts Brian C BC Yu Xue-Zhong XZ

Frontiers in immunology 20190508

Allogeneic hematopoietic cell transplantation (allo-HCT) is performed with curative intent for high- risk blood cancers and bone marrow failure syndromes; yet the development of acute and chronic graft-vs.-host disease (GVHD) remain preeminent causes of death and morbidity. The IL-12 family of cytokines is comprised of IL-12, IL-23, IL-27, IL-35, and IL-39. This family of cytokines is biologically distinct in that they are composed of functional heterodimers, which bind to cognate heterodimeric ...[more]

PMID: 31139181

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Project description:Mycetoma is a neglected tropical disease, endemic in many tropical and subtropical regions, characterised by massive deformity and disability and can be fatal if untreated early and appropriately. Interleukins (IL) -35 and IL-37 are newly discovered cytokines that play an important role in suppressing the immune system. However, the expression of these interleukins in patients with Madurella mycetomatis (M. mycetomatis) induced eumycetoma has not yet been explored. The aim of this study is to determine the levels of IL-1 family (IL-1β, IL-37) and IL-12 family (IL-12, IL-35) in a group of these patients and the association between these cytokines levels and the patients' demographic characteristics. The present, case-control study was conducted at the Mycetoma Research Centre, Soba University Hospital, University of Khartoum, Sudan and it included 140 individuals. They were divided into two groups; group I: healthy controls [n = 70; median age 25 years (range 12 to 70 years)]. Group II: mycetoma patients [n = 70 patients; median age 25 (range 13 to 70 years)]. Cytokines levels were measured in sera using enzyme linked immunosorbent assay (ELISA). There was a significant negative correlation between IL-1β and IL-12 levels and lesion size and disease duration, while IL-37 and IL-35 levels were significantly positively correlated with both lesion size and disease duration. The analysis of the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a negative significant association with IL-1β cytokine, where a unit increment in IL-1β will decrease the levels of IL-37 by 35.28 pg/ml. The levels of IL-37 among the patients with a duration of mycetoma infection ≤ 1 year were significantly low by an average of 18.45 pg/ml compared to patients with a mycetoma infection's duration of ≥ 5years (reference group). Furthermore, the risk factors of higher levels of IL-35 in mycetoma patients revealed a negative significant association with IL-12, as a unit increment in IL-12 decreases the levels of IL-35 by 8.99 pg/ml (p < 0.001). Levels of IL-35 among the patients with duration of mycetoma infection ≤ one year were significantly low on average by 41.82 pg/ml (p value = 0.002) compared to patients with a duration of mycetoma infection ≥ 5 years (reference group). In conclusion, this study indicates that both IL-35 and IL-37 are negatively associated with the levels of IL-1β and IL-12 in eumycetoma mycetoma infection; and high levels of IL-37 and IL-35 may have a negative impact on disease progression.

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Dataset Information

The IL-12 Cytokine and Receptor Family in Graft-vs.-Host Disease.

Publications

The IL-12 Cytokine and Receptor Family in Graft-vs.-Host Disease.

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