Summary

The rising incidence of allergy and asthma most likely represents misdirected T helper type 2 immune responses that evolved for host-protection against parasitic helminths. Despite several decades of research, mechanisms responsible for initial development of CD4⁺T_H2 cells from naïve T cell precursors remain elusive. Epithelial cell derived cytokines such as interleukins 25, 33 (IL-25, IL-33) and thymic stromal lymphopoietin (TSLP) have been implicated in driving T_H2 polarization, but the initial stimuli that cause release of these cytokines is entirely unclear. In this study, new evidence will be discussed that shows how trefoil factors (TFF), mucus-associated proteins, are a critical first-step in differentiation of T_H2 cells through mechanisms dependent upon alternative macrophage activation.  Data will be presented in mouse models of infection with the hookworm Nippostrongylus brasiliensis and IL-13-dependent murine asthma.  This work provides a potential mechanism to explain how T cell differentiation is shaped by innate immune responses that occur rapidly following pathogen infestation within the intestinal and lung mucosa.

Dr.DeBrobski Herbert poster  pptx.pdf