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TH2 cells in the pathogenesis of airway remodeling

Regulatory T cells a plausible panacea for asthma

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Abstract

T-helper type 2 (TH2) cells are one of the hallmarks of airway remodeling. The daunting task of regaining tolerance will be to regulate airway hyperresponsiveness (AHR) and remodeling in chronic asthma by balancing the ballet of TH1 and TH2 cells. The mechanism of tolerance appears to be modulated by a specialized subset of T cells called regulatory T cells (Tregs). Currently there are six subtypes of Tregs including CD4+CD25+ naturally occurring (N-Tregs), inducible naïve CD4+CD25T cells (TR1), TR1 memory phenotype, T-helper type 3 (TH3), CD4CD25+DX5+ natural killer T cells (TRNKT), and CD4CD25+CD8+ cytotoxic T cells (TRCTC). The development of Tregs is controversial as to whether they occur in the thymus or peripheral lymphoid tissue. Studies have shown that N-Tregs are generated in the thymus and TR1 cells occur in the periphery. Nevertheless, Tregs express an arsenal of molecular membrane markers: CD3, CD25, CD62L, CD69, BTLA, GITR, ICOS, Neuroplin-1 (Nrp-1), and PD-1. However, the most definitive marker is Forkhead Winged-Helix Transcriptional Factor Box p3 (Foxp3). The suppression of N-Tregs occurs by cell-to-cell contact, and low levels of IL-10 and moderate levels of TGF-β, but the primary mechanism involves the sequestration and activation of neighboring naïve CD4+CD25T cells to become TR1 cells. In contrast, TR1 cells exert their suppressive properties by copious secretion of IL-10 and TGF-β. These suppressive mechanisms occur by the inhibition of IL-2 production and the promotion of cell cycle arrest. The development of this specialized subset of T cells is an enigma, but their understanding will provide a plausible panacea for asthma.

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McGee, H.S., Agrawal, D.K. TH2 cells in the pathogenesis of airway remodeling. Immunol Res 35, 219–231 (2006). https://doi.org/10.1385/IR:35:3:219

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Key Words

  • Airway remodeling
  • Asthma
  • Fox P3
  • Inflammatory cytokines
  • PD-1
  • Th-2 cells
  • T-regulatory cells
  • TR-1 cells