Browsing by Author "Hummel, Sarah A."

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    IL-10–producing Tfh cells accumulate with age and link inflammation with age-related immune suppression
    (American Association for the Advancement of Science, 2020-07-29) Almanan, Maha; Raynor, Jana; Ogunsulire, Ireti; Malyshkina, Anna; Mukherjee, Shibabrata; Hummel, Sarah A.; Ingram, Jennifer T.; Saini, Ankur; Xie, Markus M.; Alenghat, Theresa; Way, Sing Sing; Deepe, George S.; Divanovic, Senad; Singh, Harinder; Miraldi, Emily; Zajac, Allan J.; Dent, Alexander L.; Hölscher, Christoph; Chougnet, Claire; Hildeman, David A.; Microbiology and Immunology, School of Medicine
    Aging results in profound immune dysfunction, resulting in the decline of vaccine responsiveness previously attributed to irreversible defects in the immune system. In addition to increased interleukin-6 (IL-6), we found aged mice exhibit increased systemic IL-10 that requires forkhead box P3–negative (FoxP3−), but not FoxP3+, CD4+T cells. Most IL-10–producing cells manifested a T follicular helper (Tfh) phenotype and required the Tfh cytokines IL-6 and IL-21 for their accrual, so we refer to them as Tfh10 cells. IL-21 was also required to maintain normal serum levels of IL-6 and IL-10. Notably, antigen-specific Tfh10 cells arose after immunization of aged mice, and neutralization of IL-10 receptor signaling significantly restored Tfh-dependent antibody responses, whereas depletion of FoxP3+ regulatory and follicular regulatory cells did not. Thus, these data demonstrate that immune suppression with age is reversible and implicate Tfh10 cells as an intriguing link between “inflammaging” and impaired immune responses with age.
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    Paracrine IL-2 Is Required for Optimal Type 2 Effector Cytokine Production
    (American Association of Immunologists, 2017-06-01) Olson, Matthew R.; Ulrich, Benjamin J.; Hummel, Sarah A.; Khan, Ibrahim; Meuris, Brice; Cherukur, Yesesri; Dent, Alexander L.; Janga, Sarath Chandra; Kaplan, Mark H.; Pediatrics, School of Medicine
    IL-2 is a pleiotropic cytokine that promotes the differentiation of Th cell subsets, including Th1, Th2, and Th9 cells, but it impairs the development of Th17 and T follicular helper cells. Although IL-2 is produced by all polarized Th subsets to some level, how it impacts cytokine production when effector T cells are restimulated is unknown. We show in this article that Golgi transport inhibitors (GTIs) blocked IL-9 production. Mechanistically, GTIs blocked secretion of IL-2 that normally feeds back in a paracrine manner to promote STAT5 activation and IL-9 production. IL-2 feedback had no effect on Th1- or Th17-signature cytokine production, but it promoted Th2- and Th9-associated cytokine expression. These data suggest that the use of GTIs results in an underestimation of the presence of type 2 cytokine-secreting cells and highlight IL-2 as a critical component in optimal cytokine production by Th2 and Th9 cells in vitro and in vivo.