Trained Immunity Induced by in Vivo Peptide-Based STAT6 Inhibition Prevents Ragweed Allergy in Mice
Background
Allergic airways disease (AAD) is initiated, maintained by the type 2 (T2) inflammatory pathway, and is partially regulated by cytokines IL-4 and IL-13 following activation of the STAT6 transcription factor.
Objective
To investigate mucosal immune responses, using neonatal vaccination with the STAT6 inhibitory peptide (STAT6-IP), to prevent the development of ragweed-induced AAD.
Methods
We demonstrate that transfer of CD4+ T cells or dendritic cells (DC) from STAT6-IP vaccinated wild-type BALB/c mice to naïve mice, that were subsequently chronically exposed to sensitizing doses of ragweed allergen, is sufficient to prevent development of T2 responses in recipients.
Results
Our results demonstrate significant reductions in; airways hyperresponsiveness (AHR); ragweed-specific IgE; pulmonary inflammation; T2 cytokines; and inflammatory gene expressions in recipient mice. Expression of IDO, TGFβ and T regulatory cells were all significantly increased. Anti-TGFβ treatment during the ragweed sensitization phase re-constituted the pro-inflammatory T2 immune response. We show that tolerance can be attained via DC or T cells trained in the STAT6-IP-mediated tolerant milieu. This effect is not restricted to a particular allergen and does not require antigen-mediated T cell activation prior to transfer.
Conclusion
These data indicate that early transient STAT6-inhibition constitutes an effective immunomodulatory airways allergy preventative strategy.
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Posted 09 Dec, 2020
Received 23 Jan, 2021
Received 14 Jan, 2021
On 04 Jan, 2021
On 03 Jan, 2021
Invitations sent on 28 Dec, 2020
On 02 Dec, 2020
On 02 Dec, 2020
On 02 Dec, 2020
On 01 Dec, 2020
Trained Immunity Induced by in Vivo Peptide-Based STAT6 Inhibition Prevents Ragweed Allergy in Mice
Posted 09 Dec, 2020
Received 23 Jan, 2021
Received 14 Jan, 2021
On 04 Jan, 2021
On 03 Jan, 2021
Invitations sent on 28 Dec, 2020
On 02 Dec, 2020
On 02 Dec, 2020
On 02 Dec, 2020
On 01 Dec, 2020
Background
Allergic airways disease (AAD) is initiated, maintained by the type 2 (T2) inflammatory pathway, and is partially regulated by cytokines IL-4 and IL-13 following activation of the STAT6 transcription factor.
Objective
To investigate mucosal immune responses, using neonatal vaccination with the STAT6 inhibitory peptide (STAT6-IP), to prevent the development of ragweed-induced AAD.
Methods
We demonstrate that transfer of CD4+ T cells or dendritic cells (DC) from STAT6-IP vaccinated wild-type BALB/c mice to naïve mice, that were subsequently chronically exposed to sensitizing doses of ragweed allergen, is sufficient to prevent development of T2 responses in recipients.
Results
Our results demonstrate significant reductions in; airways hyperresponsiveness (AHR); ragweed-specific IgE; pulmonary inflammation; T2 cytokines; and inflammatory gene expressions in recipient mice. Expression of IDO, TGFβ and T regulatory cells were all significantly increased. Anti-TGFβ treatment during the ragweed sensitization phase re-constituted the pro-inflammatory T2 immune response. We show that tolerance can be attained via DC or T cells trained in the STAT6-IP-mediated tolerant milieu. This effect is not restricted to a particular allergen and does not require antigen-mediated T cell activation prior to transfer.
Conclusion
These data indicate that early transient STAT6-inhibition constitutes an effective immunomodulatory airways allergy preventative strategy.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5