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Journal Article
Repositioning TH cell polarization from single cytokines to complex help
2021
Overview
When helper T (T
H
) cell polarization was initially described three decades ago, the T
H
cell universe grew dramatically. New subsets were described based on their expression of few specific cytokines. Beyond T
H
1 and T
H
2 cells, this led to the coining of various T
H
17 and regulatory (T
reg
) cell subsets as well as T
H
22, T
H
25, follicular helper (T
FH
), T
H
3, T
H
5 and T
H
9 cells. High-dimensional single-cell analysis revealed that a categorization of T
H
cells into a single-cytokine-based nomenclature fails to capture the complexity and diversity of T
H
cells. Similar to the simple nomenclature used to describe innate lymphoid cells (ILCs), we propose that T
H
cell polarization should be categorized in terms of the help they provide to phagocytes (type 1), to B cells, eosinophils and mast cells (type 2) and to non-immune tissue cells, including the stroma and epithelium (type 3). Studying T
H
cells based on their helper function and the cells they help, rather than phenotypic features such as individual analyzed cytokines or transcription factors, better captures T
H
cell plasticity and conversion as well as the breadth of immune responses in vivo.
The T helper subset paradigm has been instrumental in informing our understanding of T cell diversity; however, modern single-cell analyses have revealed the limits of the concept. In their Perspective, Becher and colleagues propose an alternative framework in which to understand T helper diversity, based not on transcription factors and cytokines but rather physiological functionality.
Publisher
Nature Publishing Group US,Nature Publishing Group
