Abstract
Dendritic cells (DCs) play a key role in initiating immune responses and maintaining immune tolerance. In addition to playing a role in thymic selection, DCs play an active role in tolerance under steady state conditions through several mechanisms which are dependent on IL-10, TGF-β, retinoic acid, indoleamine-2,3,-dioxygenase along with vitamin D. Several of these mechanisms are employed by DCs in induction of regulatory T cells which are comprised of Tr1 regulatory T cells, natural and inducible foxp3+ regulatory T cells, Th3 regulatory T cells and double negative regulatory T cells. It appears that certain DC subsets are highly specialized in inducing regulatory T cell differentiation and in some tissues the local microenvironment plays a role in driving DCs towards a tolerogenic response. In this review we discuss the recent advances in our understanding of the mechanisms underlying DC driven regulatory T cell induction.
Highlights
Dendritic cells (DCs) are professional antigen presenting cells and are essential mediators of immunity and tolerance
DCs are the key players in maintaining immune tolerance, for their ablation has been shown to result in autoimmunity, highlighting the active role that DCs play under steady state conditions in maintaining immune tolerance [1]
Central tolerance in the thymus is largely mediated by cortical epithelial cells, medullary epithelial cells and thymic DCs and involves deletion of self reactive thymocytes along with induction of naturally occurring regulatory T cells (Tregs), which play a key role in maintaining self tolerance and suppressing a variety of pathological immune responses [2]
Summary
Dendritic cells (DCs) are professional antigen presenting cells and are essential mediators of immunity and tolerance. Pulmonary DCs in mice exposed to respiratory antigens undergo maturation but secrete IL10 which drives induction of Tr1 cells These Tr1 cells can suppress airway responsiveness and their development is dependent on IL-10 production by DCs, since adoptive transfer of DCs from IL-10 deficient mice fail to induce Tr1 mediated tolerance [22]. Retinoic acid producing DCs drive iTreg differentiation Oral intake of protein antigens leads to induction of oral tolerance, which is largely mediated through generation of iTregs in the mesenteric lymph nodes. Studies have shown that treatment of asthmatic mice with DP1 agonist can suppress features of asthma by acting on pulmonary DCs and inducing cAMP dependent protein kinase A activation, which suppresses the ability of DCs to drive Th2 response and instead promotes induction of iTregs [93]. The mechanisms of how DCs can prime differentiation of DN Tregs is not understood, syngeneic DCs have been successfully utilized for expansion of antigen specific DN Tregs [101]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
