Abstract
Transforming growth factor-beta 1 (TGF-β1) induces ‘effector resistance’ in the non-resistant Th17 cell subtypes 3712
The Journal of immunology (1950), Vol.214(Supplement_1), vkaf2831480
11/01/2025
DOI: 10.1093/jimmun/vkaf283.1480
Abstract
Abstract Description
Differentiation of naïve CD4 T-cells in varied cytokine combinations generates different flavors of IL-17 secreting CD4 T-helper cells (Th17). For example, combination of TGF-β1 + IL-6 generates ‘non-pathogenic’ Th17 cells, whereas IL-6 + IL-1β + IL-23 generates ‘pathogenic’ Th17 cells. We made the unexpected observation that canonical ‘non-pathogenic’ Th17s are resistant to suppression by autologous CD8 T-cells while ‘pathogenic’ Th17s are susceptible to greater suppression. Transcriptomic analysis showed upregulation of TGF-β1 pathways in ‘non-pathogenic’ Th17s. Thus, we hypothesized that TGF-β1 is the driver for attaining ‘effector resistance’. We observed that upon exposure to TGF-β1, even the ‘pathogenic’ Th17s become significantly more resistant to suppression and produce lower levels of GMCSF, CD39, IL-17F along with increased expression of transcription factors Bach2, Twist2. TGF-β1 also induces a resistance state when added as a sole cytokine to ex-vivo bulk CD4+CD25- T-cell cultures. These findings were corroborated in an in vivo model of the graft versus host disease, wherein, TGF-β1 treatment reversed the ‘pathogenic’ Th17s towards a ‘non-pathogenic’ but more ‘resistant’ phenotype. Thus, we postulate that TGF-β1 cytokine induces a functional plasticity in Th17 cells by overriding the effect of IL-1β and IL-23, further contributing to the pathogenesis of autoimmune disease relapse, particularly in the context of relapsing remitting multiple sclerosis (RRMS).
Funding Sources
Supported by grants from NIH and VA to N.J.K.
Topic Categories
Immune Response Regulation: Cellular Mechanisms (IRC)
Details
- Title: Subtitle
- Transforming growth factor-beta 1 (TGF-β1) induces ‘effector resistance’ in the non-resistant Th17 cell subtypes 3712
- Creators
- Kshitija KaleMichael Patrick Crawford - University of IowaSudeep GhimireChakrapani VemulawadaJace HeathConnor R. WilhelmAlexander W. BoydenAshutosh K. MangalamNitin Karandikar
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.214(Supplement_1), vkaf2831480
- DOI
- 10.1093/jimmun/vkaf283.1480
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- Oxford University Press
- Grant note
- NIHVA
Supported by grants from NIH and VA to N.J.K.
- Alternative title
- IMMUNOLOGY2025™ Abstracts
- Language
- English
- Date published
- 11/01/2025
- Academic Unit
- Pathology; Iowa Neuroscience Institute
- Record Identifier
- 9985035039902771
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