Dampening Inflammation and Allergy to Fungi: A Task for Treg Cells

Tregs (Chapters 5 and 9 in Immunology IV) are cells that actively control, suppress, or inhibit the function of other cells and play major roles in the pathogenesis of allergic (Chapter 18 in Immunology IV), autoimmune (Chapter 19 in Immunology IV), and infectious diseases (Chapters 12, 13, 14, and 15 in Immunology IV) and cancer (Chapter 20 in Immunology IV). Currently, a major investigative effort is being directed to their role in allergic disease (Chapter 18 in Immunology IV). CD4+ Tregs are abundant in mucosal lymphoid tissues, where they downregulate Th1 and Th2 responses.

As described previously, the inflammatory response to fungi may serve to limit infection but may also contribute to pathogenicity, as documented by the occurrence of severe fungal infections in patients with immune reconstitution inflammatory syndrome (IRIS). These patients may experience intractable fungal infections despite recovery from neutropenia with the occurrence of adaptive immune responses. The above considerations suggest that in fungal diseases, a series of complex induced immunoregulatory elements are essential and may contribute to the fine-tuning of inflammation and Th reactivity to fungi.

In this regard, CD4+ T cells are known to be comprised of a series of iTreg cells that, in contrast to the natural T cells produced in the thymus, are primed locally (Chapter 9 in Immunology IV). These iTreg cells include (1) Tr1 cells producing IL-10 and (2) Th3 cells producing transforming growth factor TGFβ. These locally induced Treg cells contribute to the immunomodulation of antimicrobial immune responses by fine-tuning and balancing the other effector axis, minimizing harmful inflammatory consequences. The final outcome of this dynamic equilibrium will not only be determined by interactions between pathogens and cells of the innate immune system, but also by the actions of these induced Tregs on the adaptive immune function. Conceptually, in a similar fashion to their effects on immunity against pathogens, Treg cells can also impede effective immunosurveillance of tumors (Chapter 20 in Immunology IV). At the present time, the concept of aberrant numbers and/or functions of Treg cells has been incorporated within the global view of counter-regulatory elements affecting self versus nonself discrimination. The Treg cell population is recognized as having great clinical applications in the outcome of infection, autoimmunity, transplantation, cancer, and allergic disease.

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