Regulatory T Cells Developing Peri-Weaning Are Continually Required to Restrain Th2 Systemic Responses Later in Life.

Atopic disorders including allergic rhinitis, asthma, food allergy, and dermatitis, are increasingly prevalent in Western societies. These disorders are largely characterized by T helper type 2 (Th2) immune responses to environmental triggers, particularly inhaled and dietary allergens. Exposure to such stimuli during early childhood reduces the frequency of allergies in at-risk children. These allergic responses can be restrained by regulatory T cells (Tregs), particularly Tregs arising in the gut. The unique attributes of how early life exposure to diet and microbes shape the intestinal Treg population is a topic of significant interest. While imprinting during early life promotes the development of a balanced immune system and protects against immunopathology, it remains unclear if Tregs that develop in early life continue to restrain systemic inflammatory responses throughout adulthood. Here, an inducible deletion strategy was used to label Tregs at specified time points with a targeted mechanism to be deleted later. Deletion of the Tregs labeled peri-weaning at day of life 24, but not before weaning at day of life 14, resulted in increased circulating IgE and IL-13, and abrogated induction of tolerance towards new antigens. Thus, Tregs developing peri-weaning, but not before day of life 14 are continually required to restrain allergic responses into adulthood.
Competing Interests: RN, KK, and KM are inventors on U.S. Nonprovisional Application Serial No. 15/880,658 Compositions and Methods for Modulation of Dietary and Microbial Exposure. PT discloses a financial conflict of interest with MediBeacon Inc (member of their Scientific Advisory Board, consultant, and equity holder), is a consultant to Kallyope Inc., and is a potential recipient of royalties from a patent to test human gut permeability noninvasively. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Knoop, McDonald, Hsieh, Tarr and Newberry.)