@article{e1687e5fb1d64bd5b90d287c88ff4636,
title = "Synchronization of mothers and offspring promotes tolerance and limits allergy",
abstract = "Allergic disorders, characterized by Th2 immune responses to environmental substances, are increasingly common in children in Western societies. Multiple studies indicate that breastfeeding, early complementary introduction of food allergens, and antibiotic avoidance in the first year of life reduces allergic outcomes in at-risk children. Why the benefit of these practices is restricted to early life is largely unknown. We identified a preweaning interval during which dietary antigens are assimilated by the colonic immune system. This interval is under maternal control via temporal changes in breast milk, coincides with an influx of naive T cells into the colon, and is followed by the development of a long-lived population of colonic peripherally derived Tregs (pTregs) that can be specific for dietary antigens encountered during this interval. Desynchronization of mothers and offspring produced durable deficits in these pTregs, impaired tolerance to dietary antigens introduced during and after this preweaning interval, and resulted in spontaneous Th2 responses. These effects could be rescued by pTregs from the periweaning colon or by Tregs generated in vitro using periweaning colonic antigen-presenting cells. These findings demonstrate that mothers and their offspring are synchronized for the development of a balanced immune system.",
author = "Knoop, {Kathryn A.} and McDonald, {Keely G.} and Coughlin, {Paige E.} and Kulkarni, {Devesha H.} and Gustafsson, {Jenny K.} and Brigida Rusconi and Vini John and {Malick Ndao}, I. and Avraham Beigelman and Misty Good and Warner, {Barbara B.} and Elson, {Charles O.} and Hsieh, {Chyi Song} and Hogan, {Simon P.} and Tarr, {Phillip I.} and Newberry, {Rodney D.}",
note = "Funding Information: The authors would like to thank Mark J. Miller for assistance with 2P imaging and analysis (MJM). The 2P imaging was performed at the In Vivo Imaging Core at Washington University School of Medicine. The Washington University Digestive Diseases Research Center Core, supported by NIH grant P30 DK052574, provided the germ-free mice. The High Speed Cell Sorter Core at the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, Missouri, USA — supported in part by NCI Cancer Center Support Grant P30 CA91842 — provided flow cytometric cell sorting services. The Speed Congenics Facility of the Rheumatic Diseases Core Center, supported by NIH grant P30AR048335 bred the Myd88–/–mice onto the C57BL/6 background. This work was supported by the following grants: DK097317 (RDN), AI131342 (RDN and PIT), AI140755, and AI136515 (RDN and CSH); AI112626 (SPH and RDN); DK071176 (COE); DK052574 and DK125606 (BR); DK109006 and AI095542 (KAK); K08DK101608, R03DK111473, and R01DK118568 (MG); March of Dimes Foundation grant 5-FY17-79 (MG); and the Children{\textquoteright}s Discovery Institute grants MI-FR-2017-596 (MG) and MD-II-2018-725 (BBW). Publisher Copyright: Copyright: {\textcopyright} 2020, American Society for Clinical Investigation.",
year = "2020",
month = aug,
day = "6",
doi = "10.1172/jci.insight.137943",
language = "English",
volume = "5",
journal = "JCI Insight",
issn = "2379-3708",
number = "15",
}