The origin of DCs and capacity for immunologic tolerance in central and peripheral tissues

Abstract

Dendritic cells (DCs) are specialized immune sentinels that play key role in maintaining immune homeostasis by efficiently regulating the delicate balance between protective immunity and tolerance to self. Although DCs respond to maturation signals present in the surrounding milieu multiple layers of suppression also co-exist that reduce the infringement of tolerance against self-antigens. These tolerance inducing properties of DCs are governed by their origin and a range of other factors including distribution, cytokines, growth factors, and transcriptional programing, that collectively impart suppressive functions to these cells. DCs directing tolerance secrete anti-inflammatory cytokines and induce naïve T cells or B cells to differentiate into regulatory T cells (Tregs) or B cells. In this review, we provide a detailed outlook on the molecular mechanisms that induce functional specialization to govern central or peripheral tolerance. The tolerance-inducing nature of DCs can be exploited to overcome autoimmunity and rejection in graft transplantation.

Novel immune signatures associated with dysplastic naevi and primary cutaneous melanoma in human skin

“…Recent literature has shown that the presence of increased lymphocytic infiltrates in MM alone may not be as significant as the functional activity of these cells in combating MM . Thus, we queried immune cell–specific gene transcript signatures, which revealed progressive increases in exhausted T cells, regulatory T cells (Tregs) and tolerogenic dendritic cells (DCs) gene signatures (Figure A‐C). RT‐PCR confirmed progressive increases in Treg activity (TGF‐β and IL‐10) and immunoregulatory markers (CTLA‐4, PD‐L1, PD‐L2 and IDO1) associated with exhausted T cells (Figure D‐I).…”

“…SOCS3 expression by dendritic cells has not previously been described in human melanoma. Increased cytokine IL‐10 in the immune microenvironment has been reported to increase SOCS3 expression and IL‐10 secretion by DCs, which prolong Treg cell function . Treg cells, in turn, contribute to T‐cell exhaustion, which mount ineffective immune responses against cancer.…”

“…Recent literature has shown that the presence of increased lymphocytic infiltrates in MM alone may not be as significant as the functional activity of these cells in combating MM. [37] Thus, we queried immune cell-specific gene transcript signatures, [38][39][40][41] which revealed progressive increases in exhausted T cells, regulatory T cells (Tregs) and tolerogenic den-…”

Near-Infrared 1064 nm Laser Modulates Migratory Dendritic Cells To Augment the Immune Response to Intradermal Influenza Vaccine

“…An accumulating body of evidence demonstrates that different DC subsets are responsible for specialized immune functions. DCs imprint naïve responses to direct the differentiation of CD4 helper T cells into T H 1, T H 2, T H 17, Tfh, Tr1, and Treg (9–14). Multiple specialized subtypes of DCs that have been identified can be distinguished by surface markers, which have recently been correlated to their unique transcriptome based programs across mice and humans (15–21).…”

Dendritic cells in autoimmunity, infections, and cancer

“…Devi and Anandasabapathy review the development of tolerogenic DCs in different tissues and provide and exhaustive evaluation of the transcriptional programs that control them (4). Finally, one of the best-characterized tolerogenic functions of DCs is the promotion of Treg differentiation.…”