Name:

The Innate Immune System:

Institution:
Date:


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Abstract
The innate immune system consists of cell networks which provide earliest detection of pathogens in
the body .This paper highlights a study by Mascanfroni et al. (2013), on how IL-27 acts on DCs to
suppress T cell response and its relation with autoimmunity providing its key findings and implications
in immunology.

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The Innate Immune System
Interleukin 27(IL-27) is a vital cytokine, which regulates the immune responses in the body. It
is composed of the product of Epstein-Barr virus induced gene 3, and is structurally related to IL-12
(Mascanfroni et al., 2013). Autoimmunity is an emerging field in which main interest is the area of the
bodys anomalous response, fighting its own cells. The body responds to foreign organisms in various
ways, including producing T cells. Owing to their effect on both regulatory and effector T cells in vivo,
the study of dendritic cells (DCs) is vital. Immunity is a crucial element in human life.
What are the mechanisms of disease pathogenesis? What pathways contribute to the regulation
of DCs activities in autoimmunity? These are some of the key concerns in this study. Results of this
study would assist in the quest for the development of novel therapeutic approaches and efficacious
interventions (Mascanfroni et al., 2013).
IL-27 signaling in DCs on affects the differentiation of T (reg) cells, CNS autoimmunity, and T
cells. One major finding in this research was that the introduction of CD39 in DCs helped to mediate
the effect of IL27. Additionally, IL-27 signaling in DCs of mousses limited effector cell generations for
helper T cells subsets, T
H
1 and T
H
17, and development of experimental autoimmune encephalomyelitis
(EAE). The study discovered that IL-27-induced CD39 led to a decline of ATP extracellular
concentration and reduced nucleotide-dependent activation of NLRP3 inflammasome. In addition,
vaccinations, which involved the use of dendritic cells conditioned with IL-27 suppressed the
established relapsing-remitting EAE (Mascanfroni et al., 2013).
The conclusions of the study were, IL-27 in DCs significantly contributes to development of
autoimmunity as well as limiting the responses if pathogenic T cells. Multiple sclerosis (MS) seemed to
produce high quantities of T
H
1- and T
H
17- cytokines, supporting the idea that DCs promote pathogenic
T cell response in such patients. T
H
1 and T
H
17 subsets of T cells were responsible for the development
of autoimmunity and inflammation of tissue in the body. Further, the study found that IL-27 signaling
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in DCs up regulated expression of the immunoregulatory molecule CD39 (encoded by Entpd1) and
limited the development of EAE. CD39, expressed by conventional DCs (cDCs), reduced the
extracellular concentration of ATP and decreased ATP-triggered activation of the NLRP3
inflammasome. Moreover, the study established that vaccination of mice with IL-27-conditioned DCs
suppressed established chronic relapsing-remitting EAE. Together, the existing data demonstrated that
IL-27 signaling in DCs controls the pathogenic T cell responses in a CD39-dependent manner and
identify IL-27-conditioned DCs as a possible approach for the treatment of disorders mediated by the
immune system (Mascanfroni et al., 2013).
Studies on the association of CD39 and immunity have shown varying results. A study by
Husler et al demonstrated that CD39 and CD73 ectonucleotides degrade the immune stimulating to
adenosine. Eventually, they inhibit NK and T cell responses through A(2A) adenosine receptor
(ADORA2A).This mechanism is incorporated by regulatory T cells (T(reg)) which are associated with
increased mortality in Ovarian cancer (OvCA). The conclusion of this study was that both CD39 and
CD73 ectonucleotides and ADORA2A are possible targets for new treatments in OvCA, which not
only affects the functions of T(reg) but also relieve internal immunosuppressive feature of stromal and
tumor cells. The study also revealed that CD39 was required for effective modulation of the antigen
presenting function of cDCs by IL-27 in vitro and in vivo. IL-27 was responsible for the up regulation
of expression of additional immunoregulatory such as IFN-, IDO, TGF- and IL-27 itself (P 1061)
(Mascanfroni et al., 2013).
A study by Kumar & Sharma (2010) showed that neutrophils contribute to the effectiveness of
the immune system by regulating the immune response. Neutrophil extracellular traps and anti-
microbial molecules are released to contain the inflammations and infections that invade an organism.
Additionally, the neutrophils are responsible for producing the relevant alerts and signals for the
maturation and activation of dendritic cells and macrophages. Furthermore, it is the neutrophils, which
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are responsible for the regulation of T-cell responses against tumor antigens and pathogens (Kumar &
Sharma, 2010).
DCs are responsible for the control of some mechanisms of the autoimmunity of the central
nervous system(CNS).DCs promote the differentiation and activation of the pathogenic T cells in the
central nervous system; promote entry of T cells into the CNS; and diversification of new CNS
epitopes autoimmune response (Mascanfroni et al., 2013). Dendritic cells significantly affect the
effectiveness of the innate immune system. One study revealed that, Mesenchymal Stem Cells (MSCs)
could inhibit dendritic cells from optimally producing T cells (Chiesa 2011).A study by Sattler et al.,
showed that CD-39 is expressed together with CD73 on murine mesenchymal stromal cells catalyzing
the generation of adenosine, which can directly act on the activated T cells through adenosine A2A
receptor. Hence, CD39/CD73 expression is important for murine MSCs immunoregulatory functions
(Sattler, 2011). Mesenchymal cells have potential for immunoregulation in the body. They inhibit the
proliferation of T cells and maturation of DCs. This makes Mesenchymal stem cells (MSCs) promising
for future clinical applications such the treatment and prevention of bone marrow rejection and
autoimmune maladies. Various studies have examined immunosuppressive factors contributing to the
immunosuppressive effect of MSCs. The findings provide critical information concerning
immunosuppression of MScs, giving guidance on how MSCs can be applied in treating disorders of the
immune system (Lisiany, 2013).
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Figure 1 below shows the result obtained by the study, showing that IL-27 controls the activity of
cDCs (Mascanfroni et al., 2013).


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Various studies have indicated that IL-27 is also responsible for certain conditions. For
example, a study by Angata et al., on the association of IL-27 and chronic obstructive pulmonary
disease revealed that, IL-27 might be mechanistically involved in worsening of COPD and potentially
serves as a systemic biomarker for the exacerbation (Angata et al., 2014). Further, an investigation into
the modulative role of IL-27 sepsis-induced impairment of lung antibacterial defense, concluded that
IL-27 was a key mediator in the defense (Cao et al., 2014)
Further, studies on the association between vitamin D and production of T cells have shown that
vitamin D directly affect the activation of T-cells. In their study of vitamin D and the molecular actions
detected in the immune system, Kamen and Tangpricha (2010) found that the recent discovery of
vitamin D receptor (VDR) shed more light in understanding innate immune mechanisms. They found
that early clinical and epidemiologic studies of animals immunity gave evidence of a clear role of
vitamin D in maintaining balance of the immune system. Cathelisicidin anti-microbial peptide was seen
to be up regulated by the vitamin D hormone in order to destroy pathogenic bacteria in the immune
cells (Kamen and Tangpricha, 2010).
A study on the physiological relevance and effects of IL-27 signaling in DCs on autoimmunity
and regulation of T cell response should be carried out, as this is not yet clear. The uptake of the
antibiotic bacteria and the basis behind the killing of the bacteria remain to be a question for further
study. Further study on dendritic cells could help identify the pathogenesis of disease and guide therapy
for immune system mediated disorders.

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