Targeting metabolism to regulate immune responses in autoimmunity and cancer

These GEITP pages include topics where a “signal” (from the environment; or from another cell or organ) is received by a cell, which then responds (using its genes, genome, epigenome) to that signal. Hence, this review article [see attached], which proposes to modify metabolism within specific immune cell-types, so that they are better able to combat human immune pathologies — such as autoimmune disorders, cancer, and graft-versus-host disease (GVHD). Blindly suppressing all immune and inflammatory responses

(e.g. using corticosteroids or non-steroidal anti-inflammatory drugs, NSAIDs) is very commonly used to treat these diseases, but this brute-force approach ignores the exquisite specificity and intricate regulation of the immune response (including the fact there is an initial proinflammatory phase, followed by a resolution phase; see reviews by C N Serhan for details).

Compared with other somatic cells, cells of the immune system possess distinct metabolic programs; and metabolic programming can differ substantially — even among different cell-types of the immune system. Indeed, immune cell activation, differentiation, and various functions — all have unique metabolic requirements to support both the energetic and biosynthetic demands of the diverse processes that constitute these responses. Metabolic reprogramming of immune cells is not simply a consequence of recognition and engagement, but rather plays an important and coordinated role in promoting differentiation and function.

Targeting critical metabolic pathways is emerging as a potent means to regulate immune responses. Over the past decade, there have been impressive advances in defining the interplay between these metabolic pathways, and immune signaling and function. Targeting metabolism — rather than particular cell-types or cytokines — in metabolically demanding processes such as autoimmunity, graft rejection, cancer, and uncontrolled chronic inflammation — could lead to successful strategies in controlling the pathogenesis of these complex disorders. 😊


Nat Rev Drug Discov 30 Jul 2019; doi: 10.1038/s41573-019-0032-5

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