IFN-γ–Producing T-Helper 17.1 Cells Are Increased in Sarcoidosis and Are More Prevalent than T-Helper Type 1 Cells

Abstract

Combined use of surface markers and functional assays to study CD4(+) T cells in sarcoidosis revealed a marked expansion of Th17.1 cells that only produce IFN-γ. These results suggest that Th17.1 cells could be misclassified as Th1 cells and may be the predominant producer of IFN-γ in pulmonary sarcoidosis, challenging the Th1 paradigm of pathogenesis.

Sarcoidosis and T-Helper Cells. Th1, Th17, or Th17.1?

“…The study by Ramstein and colleagues has several strengths, including the use of sophisticated immunophenotyping of rare blood and lung cell types from two different, well-characterized human cohorts (12). This approach provided a semiquantitative assessment of Th1, Th17, and Th17.1 cell populations in lung and blood compartments, and related ex vivo experiments confirmed the likely contribution of each cell type to IFN-g-mediated inflammation in sarcoidosis.…”

“…The study by Ramstein and colleagues builds on growing evidence that "not all Th17 cells are created equal" (12). Major insights into Th17 subset differentiation have come from mouse Supported by National Institutes of Health grants R01 HL122424 (S.N.G.…”

“…There are also some limitations in the present report, including that the authors relied on surface chemokine receptor expression to identify Th17. Th cells into canonical Th1 or Th17 subsets is not sufficient to explain this complex human disease, and that if replicated in other studies, sarcoidosis might be better considered a "Th17.1 disease" (12). Second, if Th17.1 cells are pathogenic in sarcoidosis, then combined antagonism of Th1/Th17 pathways may be needed to achieve therapeutic efficacy in humans.…”

“…1281-1291) used multiparameter flow cytometry to analyze bronchoalveolar lavage (BAL) T cells and report that a subset of Th17 cells that coexpress IFN-g is particularly enriched in the lung in sarcoidosis (12). IFN-g-producing Th17 cells (termed Th17.1 or Th17/Th1 cells) were previously detected in mouse and man, including in human subjects with sarcoidosis or Crohn's disease (13)(14)(15).…”

“…IFN-g-producing Th17 cells (termed Th17.1 or Th17/Th1 cells) were previously detected in mouse and man, including in human subjects with sarcoidosis or Crohn's disease (13)(14)(15). Ramstein and colleagues identified Th17.1 cells by their coexpression of the chemokine receptors CCR6 and CXCR3, which had been previously linked with Th17 and Th1 cells, respectively (12). IFN-g production by these CCR6 …”