Crosstalk between Interleukin-1β and Type I Interferons Signaling in Autoinflammatory Diseases

Abstract

Interleukin-1β (IL-1β) and type I interferons (IFNs) are major cytokines involved in autoinflammatory/autoimmune diseases. Separately, the overproduction of each of these cytokines is well described and constitutes the hallmark of inflammasomopathies and interferonopathies, respectively. While their interaction and the crosstalk between their downstream signaling pathways has been mostly investigated in the frame of infectious diseases, little information on their interconnection is still available in the context of autoinflammation promoted by sterile triggers. In this review, we will examine the respective roles of IL-1β and type I IFNs in autoinflammatory/rheumatic diseases and analyze their potential connections in the pathophysiology of some of these diseases, which could reveal novel therapeutic opportunities.

Inhibition of caspase pathways limits CD4+ T cell loss and restores host anti-retroviral function in HIV-1 infected humanized mice with augmented lymphoid tissue

“…We should note that of the potential list of HIV host restriction factors investigated in this experiment, the factors listed are likely only a small subset of critical factors in HIV infection as many more have yet to be identified and their implications explored. We have yet to elucidate the cellular mechanisms associated with these newly identified changes, but they could be due to the lack of inflammatory interference with type-1 interferon signaling [ 64 ].…”

“…These results may suggest that inhibition of caspase 1/4 may drive greater pro-inflammatory cytokine pathways as part of a feedback process. Given the crosstalk among IL-1β and Type I IFN pathways, the observed increase in host restriction factors following VX-765 treatment may reflect a stronger type I IFN response as a therapeutic benefit of limiting bioactive IL-1β [ 64 ]. Importantly, these changes in pro-inflammatory signatures due to caspase 1/4 inhibition were associated with diminished cell death pathway activation, preservation of CD4 + T cells, and reduced viral replication in HIS mice infected with HIV.…”

Type-I interferons promote innate immune tolerance in macrophages exposed to Mycobacterium ulcerans vesicles

“…For example, It can promote inflammation thus conferring protection during Pneumococcal Invasive Disease [ 50 ]. On the other hand, type I IFNs are also able to downregulate the inflammation, notably through the induction of IL-1Ra–an antagonist of the IL-1β receptor–and IL-10 [ 51 ], or by inhibiting the activation of the NLRP3 inflammasome [ 52 ]. This anti-inflammatory property of type I IFNs can be detrimental for the host.…”

State of the Art of Innate Immunity—An Overview

“…The review of P. Georgel provides some examples of autoimmune/autoinflammatory diseases caused by the deregulated expression of type I interferons and interleukin-1β. The role of interleukin-1 and type I interferons and their crosstalk in autoinflammatory diseases such as rheumatic diseases are analyzed to reveal novel therapeutic opportunities [ 5 ].…”