About this Research Topic
Controlling nutrient availability is essential to the regulation of several central biological processes. Enzymes that catabolize essential or semi-essential amino acids and produce biologically active metabolites have been recycled during evolution to participate in the limitation of the activation and proliferation of immune cells.
Over the years, the recognition of the importance of this family of amino-acid catabolizing enzymes in the function of the immune system has been hampered by several difficulties: i) they play partially redundant roles, although they can also be complementary and synergistic; ii) they present immune and non-immune properties; iii) their transcriptional (and sometimes post-transcriptional) regulation is complex; iv) the effects of the catabolites derived from their enzymatic reactions are diverse and context-dependent; v) they can be endowed with biological roles independent from their enzymatic activity; vi) and finally, some of these characteristics are different between mouse and human, thus complicating the interpretation of results obtained in mouse models.
Despite all these obstacles, the number of publications mentioning the leading members of this family, i. e. indoleamine 2,3-dioxygenase (IDO), type 1 arginase and inducible nitric oxide synthase (iNOS), is considerable and covers various fields of immunopathology, including the response to infectious agents, autoimmune diseases and anti-tumour immunity.
These enzymes are expressed by cells from the innate immune system, mostly from the myeloid lineage, in response to various proinflammatory signals associated with Th1 and/or Th2 responses. For example, IDO has been recognized as an important regulator of the stimulatory function of dendritic cells, controlling effector T cell activation and promoting regulatory T cell differentiation. Overexpression of IDO is associated with escape from the immune response of tumors and pathogens in several mouse models. Conversely, defective induction of IDO during chronic inflammation can participate in the rupture of peripheral tolerance to self. Furthermore, accruing evidence indicates that arginine-catabolizing enzymes, mainly nitric oxide synthases and arginases, are closely integrated with the control of immune response under physiological and pathological conditions. Myeloid cells are major players that exploit the regulators of arginine metabolism to mediate diverse, although often opposing, immunological and functional consequences. On the other hand, Interleukin-4-induced gene (IL4I1) is expressed in monocytes/macrophages and dendritic cells present in chronic Th1 inflammation and tumors, limiting T lymphocyte activation and proliferation, in part via the production of H2O2.
The aim of this Research Topic is to enlighten the readers on the latest advances of scientific knowledge regarding the role of amino acid-catabolizing enzymes in controlling normal and pathological immune responses. We propose to position these enzymes in the general context of immune regulatory systems and checkpoints, and to recapitulate the main data supporting their use as therapeutic targets in human pathology.
We welcome authors to submit Original Research, Comments and Review articles, focusing on, but not limited to, the following enzymes:
1. The tryptophan-catabolizing enzymes IDO and TDO
2. The arginine catabolizing enzymes iNOS and arginase
3. The phenylalanine oxidase IL4I1
We welcome work that concerns the regulation of the expression of these enzymes, mechanisms used by these enzymes to regulate the immune response and/or the role of these enzymes in infectious diseases, autoimmunity and/or cancer.
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.