Damage-associated molecular patterns and their role as initiators of inflammatory and auto-immune signals in systemic lupus erythematosus

Abstract

Damage-associated molecular patterns (DAMPs) are endogenous molecules that are released into the extracellular space under conditions of activation, cellular stress, or tissue damage. These molecules are recognized by pattern-recognition receptors (PRRs) and can induce inflammation and immune responses in the absence of infection. An increasing number of DAMPs have been linked to the pathogenesis of many auto-immune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis, and systemic sclerosis (SSc); as they promote the maturation/activation of different immune cells and pro-inflammatory cytokines production associated with these diseases. Several studies suggest that the loss of tolerance to self-antigens in these diseases could be due to continuous exposure to DAMPs. Thus, understanding the mechanisms of sterile inflammation triggered by DAMPs is important to elucidate novel therapeutic strategies for the treatment of various auto-immune diseases through inhibition or modulation the expression of these molecules. To this end, this review describes different DAMPs, their molecular characteristics, their modifications, and the receptors through which they activate an immune response while considering their role in the pathogenesis of various auto-immune diseases.

MicroRNA-30e-5p has an Integrated Role in the Regulation of the Innate Immune Response during Virus Infection and Systemic Lupus Erythematosus

“…Our observation for induction of miR-30e and subsequent heightened innate immune responses upon viral infection or pure PAMPs stimulation prompted us to investigate the ability of host DAMPs for induction of miR-30e because sustained DAMPs production in the host can lead to enhanced sterile inflammation and subsequently it might establish autoimmune disease ( Alvarez and Vasquez, 2017 ). To this end, ex vivo experiment was performed using hPBMCs from three healthy volunteers.…”

“…The coordinated interactions among them activate a complex cascade of signaling pathways resulting in the development of innate immune responses, for the elimination of invading microbes, through production of pro-inflammatory cytokines, type I and III interferons (IFNs), chemokines, and recruitment of immune cells, and trigger cell death ( Akira et al., 2006 ). These PRRs also sense host endogenous molecules known as damage/danger-associated molecular patterns (DAMPs) and trigger both heightened innate immune responses, including excesses interferon and cytokines production along with elevated TLRs activation, and cell death, resulting in the autoimmune disease, such lupus ( Alvarez and Vasquez, 2017 ). These signatory features were reported to promote systemic lupus erythematous (SLE) ( Yu et al., 2012 ; Devarapu and Anders, 2018 ).…”

C-type lectin receptors Mcl and Mincle control development of multiple sclerosis–like neuroinflammation

“…DAMPs, sometimes referred to as alarmins, are endogenous molecules released upon cellular activation, stress, or damage and can induce activation of inflammatory pathways through PRRs in the absence of infection. Accordingly, several DAMPs have been implicated in the pathogenesis of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, or systemic sclerosis (49,50). Among the established endogenous ligands of Mincle, SAP130 has been reported to contribute to neuroinflammation in models of cerebral hemorrhage and traumatic brain injury (30,51).…”

Tumor suppressor function of miR‑129‑5p in lung cancer

“…Preclinical data revealed that dying tumor cells emit certain danger molecular signals, known as damage-associated molecular patterns (DAMPs) (9)(10)(11)(12)(13)(14). In brief, DAMPs are intracellular sequestered biomolecules that evade recognition by the immune system under normal physiological conditions (15). However, under conditions of cellular stress or injury, these molecules are actively secreted by stressed immune cells or released from dying cells, and trigger a non-infectious inflammatory response (16).…”