Abstract
The thymus gland is a primary lymphoid organ for T-cell development. Various viral infections can result in disturbance of thymic functions. Medullary thymic epithelial cells (mTECs) are important for the negative selection of self-reactive T-cells to ensure central tolerance. Insulin-like growth factor 2 (IGF2) is the dominant self-peptide of the insulin family expressed in mTECs and plays a crucial role in the intra-thymic programing of central tolerance to insulin-secreting islet β-cells. Coxsackievirus B4 (CVB4) can infect and persist in the thymus of humans and mice, thus hampering the T-cell maturation and differentiation process. The modulation of IGF2 expression and protein synthesis during a CVB4 infection has been observed in vitro and in vivo in mouse models. The effect of CVB4 infections on human and mouse fetal thymus has been studied in vitro. Moreover, following the inoculation of CVB4 in pregnant mice, the thymic function in the fetus and offspring was disturbed. A defect in the intra-thymic expression of self-peptides by mTECs may be triggered by CVB4. The effects of viral infections, especially CVB4 infection, on thymic cells and functions and their possible role in the pathogenesis of type 1 diabetes (T1D) are presented.
Highlights
Enteroviruses (EVs) are small, non-enveloped, single-stranded, positive-sense RNA viruses that belong to the Picornaviridae family
We recently reported that the in utero coxsackievirus B4 (CVB4) infection results in a significant decrease in sj and DβTREC in both the thymus and spleen of fetus and newborns together with a decrease in intra-thymic protein tyrosine kinase 7 (PTK7) expression and T-cell accumulation within the thymus [20]
Pathogenesis, and inducing conditions suchEVs as thymic atrophy, Thymic epithelial cells (TECs) dysfunction, apoptosis, and lymphocyte this can be explained by EV-induced thymic dysfunction in the natal or perinatal life
Summary
Enteroviruses (EVs) are small, non-enveloped, single-stranded, positive-sense RNA viruses that belong to the Picornaviridae family. Stewart et al provide a link between viral infection and autoimmune diabetes by developing transgenic mice in which the insulinproducing β-cells express interferon-α (IFN-α). Local production of this antiviral cytokine by β-cells could trigger an inflammatory reaction involving the activation of natural killer. AutoreactiveEventually, T-cells that that thymic mightInbecome non- escaped thymic selection might become non- stimulated Those those autoreactive T-cells will be activated owing to the pro-inflammatory microenvironautoreactive. Molecular mimicry hascan alsostimulate been proposed as a possible mechanism of T1D, in which which a viral infection an aggressive response of T-cells. T-cell selection in the thymus can be disrupted by some viral infections [9]. Microorganisms 2021, 9, 1177 autoimmune regulator protein (AIRE), and in particular concerns, all the members of the insulin gene family [14]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
