Lynn Puddington

The overall goal of the research ongoing in my laboratory is to elucidate the contribution of maternal antigen or immune status in the susceptibility or resistance to development of allergic airway disease in offspring. It is evident from epidemiological studies that the risk for childhood asthma is increased by having a positive family history of asthma. In particular, allergic sensitization of the newborn is closely linked to maternal but not to paternal allergies. Our focus is on early life events (either pre-natal or early post-natal) that can result in T and B cell tolerance or immunity. Our hypothesis is that the environment in neonatal mice (determined by maternal immunity or passive transfer of antigen) is critical to immunological outcome, having life-long influences on development of immune responsiveness. We are identifying the cells responsible and the mechanisms by which they dictate functional commitment of the neonate to the development of, or protection from, atopy. One strategy we are undertaking to advance this work is to characterize the antigen-presenting environment in pre- and post-natal life, with the focus on defining factors that dictate whether exposure to allergen in early life induces T cell sensitization or tolerance. The thinking is that in certain circumstances, T cell sensitization can occur in utero or in early post-natal life and that factors responsible for these circumstances have increased in the past 20 years. It has been proposed that this could explain the increased incidence of asthma and other inflammatory diseases. The challenge for scientists is to identify factors that control this process, with the ultimate goal of developing therapeutic strategies to reverse the progressive increase in disease. Our studies are focused on antigen-presenting cells such as dendritic cells (DCs) or macrophages, as they are known to direct the T cell responses to antigen throughout life, presumably including the pre- and post-natal period. In addition, we have developed transgenic models for evaluating T cell functional capacity at different ages, and in different environmental conditions, e.g. spleen or lymph node vs. lung or intestine in naïve mice or those with allergic airway disease. Our findings support the concept that it is not only the innate immune system that directs T cell responses, but also that T cell responses shape the development of the innate immune system.

[2023] Retinoic acid signaling during priming licenses intestinal CD103+ CD8 TRM cell differentiation. Qiu, Zhijuan; Khairallah, Camille; Chu, Timothy H; Imperato, Jessica N; Lei, Xinyuan; Romanov, Galina; Atakilit, Amha; Puddington, Lynn; Sheridan, Brian S The Journal of experimental medicine 2023 May;220(5):