This preprint is under consideration at Allergy, Asthma & Clinical Immunology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Trained Immunity Induced by in Vivo Peptide-Based STAT6 Inhibition Prevents Ragweed Allergy in Mice
Christine T. McCusker
McGill University
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.
Keywords
Ragweed, STAT6 mucosal vaccination, allergic airways disease, asthma, murine model
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 09 Dec, 2020
No community comments so far
Review #2 received
Received 23 Jan, 2021
Review #1 received
Received 14 Jan, 2021
Reviewer #2 agreed
On 04 Jan, 2021
Reviewer #1 agreed
On 03 Jan, 2021
Reviewers invited
Invitations sent on 28 Dec, 2020
Editor assigned
On 02 Dec, 2020
Submission checks complete
On 02 Dec, 2020
Editor invited
On 02 Dec, 2020
First submitted
On 01 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
This preprint is under consideration at Allergy, Asthma & Clinical Immunology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Trained Immunity Induced by in Vivo Peptide-Based STAT6 Inhibition Prevents Ragweed Allergy in Mice
Christine T. McCusker
McGill University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 09 Dec, 2020
No community comments so far
Review #2 received
Received 23 Jan, 2021
Review #1 received
Received 14 Jan, 2021
Reviewer #2 agreed
On 04 Jan, 2021
Reviewer #1 agreed
On 03 Jan, 2021
Reviewers invited
Invitations sent on 28 Dec, 2020
Editor assigned
On 02 Dec, 2020
Submission checks complete
On 02 Dec, 2020
Editor invited
On 02 Dec, 2020
First submitted
On 01 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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