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Publications of the Week

Mucosal Viral Infection Induces a Regulatory T Cell Activation Phenotype Distinct from Tissue Residency in Mouse and Human Tissues

By July 21, 2022No Comments

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This week we profile a recent publication in Mucosal Immunology from Dr. Brianna Traxinger (pictured, front row, second from right) and the laboratories of Drs. Jennifer Lund (back row, second from right) and Martin Prlic at UW and Fred Hutch.

Can you provide a brief overview of your lab’s current research focus?

Our research focuses on elucidating mechanisms of mucosal immune protection and mucosal immunoregulation, particularly in the context of virus infection using both mouse models as well as human tissues. Current projects include defining the role of tissue-resident memory T cells and regulatory T cells during mucosal virus infection, identifying novel mucosal immune correlates of protection from HIV-1 infection, investigating immune responses and immunoregulatory mechanisms in individuals naturally infected with SARS-CoV, and discovering new genes involved in immune responses to flavivirus infection, including both Zika and West Nile viruses, using the Collaborative Cross.

What is the significance of the findings in this publication?

Our work contributes to a growing research body on mucosal tissue regulatory T cells (Tregs), demonstrating that the previously uncharacterized genitourinary tract (GU)-localized Treg population is phenotypically and functionally distinct from canonical counterparts and may perform location-specific duties.¬† As they are localized in a barrier tissue where pathogens may enter the body, GU tract (and other mucosa-localized) Tregs have large implications for the design of vaccines for sexually transmitted infections: mucosal vaccines aim to elicit robust anti-STI responses in local immune cells, so it is important to consider how Tregs may influence vaccine-induced immune responses. Furthermore, GU tract Tregs could have far-reaching implications for women’s health, as Tregs in the vagina, uterus, and cervix may influence the immune responses associated with reproductive and sexual health, such as during pregnancy.

What are the next steps for this research?

Going forward, we would like to understand how vaginal Tregs use Granzyme B (GzmB) to modulate immune responses during viral infection and interrogate the role of local Tregs during secondary exposure or reactivation of chronic STIs. We hypothesize that vaginal Tregs not only use GzmB to modulate antiviral immune responses and prevent collateral tissue damage but may also aid directly in tissue repair; however, further studies are needed. Finally, on a larger scale, we hope to see the functions of GU tract Tregs considered in mucosal vaccine design as well as in reproductive and sexual health research, as these Tregs may positively or negatively regulate GU tract immune responses in a context-dependent manner.

If you’d like us to mention your funding sources, please list them.

This work was funded by the National Institute of Allergy and Infectious Disease and training grants from the National Institutes of Health.

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