PURPOSE OF REVIEW: Regulatory T cells (Tregs) are potential therapeutic tools in averting transplant rejection and promoting lifelong tolerance. However, Tregs can be subverted by inflammatory conditions, resulting in a T helper 17 (Th17) cell response. This review looks at the relationship between Tregs and Th17 cells. RECENT FINDINGS: Both naturally occurring and transforming growth factor-beta-induced Tregs can be converted into Th17 cells in the presence of inflammatory cytokines. Transforming growth factor-beta upregulates the Treg transcription factor, forkhead box P3, as well as the Th17 transcription factor, retinoic acid receptor-related orphan receptor gamma. However, forkhead box P3 binds to retinoic acid receptor-related orphan receptor gamma, inhibiting its promotion of IL-17 gene transcription. Inflammatory cytokines can disrupt this interaction through the inhibition of forkhead box P3 expression by signal transducer and activator of transcription 3. SUMMARY: The plasticity of the Treg population during inflammation presents a challenge to the use of Tregs as a therapeutic tool in solid organ transplantation. Investigations into the Th17-Treg axis have identified a number of potential pharmacological targets to avoid the risk of conversion to Th17 cells, but further work must be done before we can separate the benefits of Treg therapy from the hazards of the Th17 response.
PURPOSE OF REVIEW: Regulatory T cells (Tregs) are potential therapeutic tools in averting transplant rejection and promoting lifelong tolerance. However, Tregs can be subverted by inflammatory conditions, resulting in a T helper 17 (Th17) cell response. This review looks at the relationship between Tregs and Th17 cells. RECENT FINDINGS: Both naturally occurring and transforming growth factor-beta-induced Tregs can be converted into Th17 cells in the presence of inflammatory cytokines. Transforming growth factor-beta upregulates the Treg transcription factor, forkhead box P3, as well as the Th17 transcription factor, retinoic acid receptor-related orphan receptor gamma. However, forkhead box P3 binds to retinoic acid receptor-related orphan receptor gamma, inhibiting its promotion of IL-17 gene transcription. Inflammatory cytokines can disrupt this interaction through the inhibition of forkhead box P3 expression by signal transducer and activator of transcription 3. SUMMARY: The plasticity of the Treg population during inflammation presents a challenge to the use of Tregs as a therapeutic tool in solid organ transplantation. Investigations into the Th17-Treg axis have identified a number of potential pharmacological targets to avoid the risk of conversion to Th17 cells, but further work must be done before we can separate the benefits of Treg therapy from the hazards of the Th17 response.
Authors: K L Pothoven; T Kheradmand; Q Yang; J L Houlihan; H Zhang; M Degutes; S D Miller; X Luo Journal: Am J Transplant Date: 2010-07-12 Impact factor: 8.086
Authors: Jeffrey J Siracuse; Mark D Fisher; Cleide G da Silva; Clayton R Peterson; Eva Csizmadia; Herwig P Moll; Scott M Damrauer; Peter Studer; Lynn Y Choi; Sanah Essayagh; Elzbieta Kaczmarek; Elizabeth R Maccariello; Andy Lee; Soizic Daniel; Christiane Ferran Journal: Transplantation Date: 2012-02-27 Impact factor: 4.939
Authors: Byung Ha Chung; Hye Jwa Oh; Shang Guo Piao; In O Sun; Seok Hui Kang; Sun Ryoung Choi; Hoon Suk Park; Bum Soon Choi; Yeong Jin Choi; Cheol Whee Park; Yong Soo Kim; Mi La Cho; Chul Woo Yang Journal: Exp Mol Med Date: 2011-11-30 Impact factor: 8.718
Authors: Ruedi K Braun; Melanie Molitor-Dart; Christopher Wigfield; Zhuzai Xiang; Sean B Fain; Ewa Jankowska-Gan; Christine M Seroogy; William J Burlingham; David S Wilkes; David D Brand; Jose Torrealba; Robert B Love Journal: Transplantation Date: 2009-12-27 Impact factor: 4.939
Authors: Khrishen Cunnusamy; Kathryn Paunicka; Nancy Reyes; Wanhua Yang; Peter W Chen; Jerry Y Niederkorn Journal: Invest Ophthalmol Vis Sci Date: 2010-08-11 Impact factor: 4.799