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2017 ; 8
(ä): 254
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Cellular and Molecular Dynamics of Th17 Differentiation and its Developmental
Plasticity in the Intestinal Immune Response
#MMPMID28408906
Bhaumik S
; Basu R
Front Immunol
2017[]; 8
(ä): 254
PMID28408906
show ga
After emerging from the thymus, naive CD4 T cells circulate through secondary
lymphoid tissues, including gut-associated lymphoid tissue of the intestine. The
activation of naïve CD4 T cells by antigen-presenting cells offering cognate
antigen initiate differentiation programs that lead to the development of highly
specialized T helper (Th) cell lineages. Although initially believed that
developmental programing of effector T cells such as T helper 1 (Th1) or T helper
2 (Th2) resulted in irreversible commitment to a fixed fate, subsequent studies
have demonstrated greater flexibility, or plasticity, in effector T cell
stability than originally conceived. This is particularly so for the Th17 subset,
differentiation of which is a highly dynamic process with overlapping
developmental axes with inducible regulatory T (iTreg), T helper 22 (Th22), and
Th1?cells. Accordingly, intermediary stages of Th17?cells are found in various
tissues, which co-express lineage-specific transcription factor(s) or cytokine(s)
of developmentally related CD4 T cell subsets. A highly specialized tissue like
that of the intestine, which harbors the largest immune compartment of the body,
adds several layers of complexity to the intricate process of Th differentiation.
Due to constant exposure to millions of commensal microbes and periodic exposure
to pathogens, the intestinal mucosa maintains a delicate balance between
regulatory and effector T cells. It is becoming increasingly clear that
equilibrium between tolerogenic and inflammatory axes is maintained in the
intestine by shuttling the flexible genetic programming of a developing CD4 T
cell along the developmental axis of iTreg, Th17, Th22, and Th1 subsets.
Currently, Th17 plasticity remains an unresolved concern in the field of clinical
research as targeting Th17?cells to cure immune-mediated disease might also
target its related subsets. In this review, we discuss the expanding sphere of
Th17 plasticity through its shared developmental axes with related cellular
subsets such as Th22, Th1, and iTreg in the context of intestinal inflammation
and also examine the molecular and epigenetic features of Th17?cells that mediate
these overlapping developmental programs.