Over the past years, immunometabolism and its role in autoimmune and autoinflammatory
disorders have become a growing Research Topic. Immunometabolism refers to studying
how cellular metabolism impacts immune cell functions and responses. Multiple factors
are contributing to the immunological response of the human immune system. Immune
cell signaling and differentiation processes control a number of metabolic pathways
in a way that determines the fate of immune cells. Pathogenesis of autoimmune disorders
is influenced by metabolic alterations of immune cells. Some immune diseases, such
as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis, have
been evidenced to exacerbate in response to metabolic alterations and dysregulation
of immune cells, including T cells, B cells, and macrophages, contributing to the
pathogenesis of the disease. On the other side, alteration of metabolic pathways in
innate immune cells, such as monocytes, neutrophils, and natural killer cells, can
contribute to excessive pro-inflammatory responses. Certain autoinflammatory disorders,
such as Schnitzler syndrome and TNF receptor-associated periodic syndrome, are attributed
to an alteration of fatty acid metabolism and mitochondrial dysfunction. However,
recognizing metabolic alterations as key contributors to disease pathogenesis, like
the immunometabolism regulators and effectors, could provide hints for novel therapeutic
targets to modulate metabolic programming and immune cell responses in autoimmune
and autoinflammatory disorders.
In this Research Topic, we aim to discuss the current challenges in immunometabolism,
particularly those attributed to autoimmune and autoinflammatory disorders, as well
as the current gaps, limitations, and prospects for developing novel therapeutic targets
against autoinflammatory disorders. The ultimate goal of this research topic is to
provide an advanced comprehension of the immuno-metabolic mechanisms interfering with
autoinflammatory disorders and explore the innovative ways of regulating the endogenous
metabolites with anti-inflammatory effects aiming to restrain the prevalence of autoimmune
and autoinflammatory disorders via specific targeting of the various metabolic events.
Rheumatoid vasculitis (RV) is an uncommon, extra-articular manifestation in patients
with long-standing seropositive rheumatoid arthritis (RA). The mean duration between
the diagnosis of RA and the onset of vasculitis is typically 10–14 years. In their
research entitled: “Peripheral ulcerative keratitis, nodular episcleritis, and pulmonary
nodules as the initial signs of rheumatic arthritis: a case report”, Wang et al. have
described a rare case of rapidly deteriorated bilateral peripheral ulcerative keratitis
(PUK) accompanied by nodular episcleritis and pulmonary nodules in a same patient
with RA but without joint involvement. The patient exhibited various symptoms, including
crescent-shaped marginal corneal ulcers in both eyes, nodular episcleritis in the
right eye, and vasculitis, confirmed by conjunctival biopsy, with positive rheumatoid
factor and anti-cyclic citrullinated protein antibody. Despite using topical and systematic
corticosteroids and other immunosuppressive medications, the ocular condition was
not relieved until the initiation of the infliximab therapy. However, PUK recurred
after discontinuing the infliximab therapy. This case highlighted the RV as a prospective
initial sign of RA. It also suggests that infliximab could be beneficial in preventing
further progression of RA-related PUK in refractory cases.
Osteoarthritis (OA) is a prevalent chronic degenerative joint disorder that manifests
a wide variety of symptoms including joint pain, stiffness, hypertrophy, deformity,
and restricted movement. Articular cartilage degradation and concomitant adaptive
osteogenesis are characteristics of OA. Liao et al., have analyzed the existing literature
on the role of autophagy in OA to identify global research trends and hotspots in
their bibliometric study entitled: “Knowledge mapping of autophagy in osteoarthritis
from 2004 to 2022: a bibliometric analysis”. Autophagy, the cellular degradation and
recycling process of cartilage, is essential in maintaining cellular homeostasis by
mediating both cell survival and apoptosis. Several researchers have focused on understanding
the mechanism underlying autophagy and OA, including AMPK, macrophages, TGF-β1 inflammatory
response, stress, and mitophagy, according to the study. The emerging research trends
focus on investigating the connection between autophagy, apoptosis, and senescence
and exploring promising drug candidates such as TXC and green tea extract. The researchers
support the trend of developing targeted drugs that enhance or restore autophagic
activity as a novel strategy for treating OA. The study thoroughly evaluates the current
literature on autophagy in OA and proposes prospective treatment options.
Perivascular adipose tissues (PVAT) were examined by Shi et al. in their work entitled:
“Perivascular Adipose Tissue Promotes Vascular Dysfunction in Murine Lupus” which
investigated the role of PVAT in systemic lupus erythematosus (SLE) and how it impacts
cardiovascular disease (CVD) in lupus patients. Using lupus mouse models, the researchers
investigated the phenotype and function of PVAT as well as the mechanisms relating
PVAT to vascular dysfunction in SLE lupus disease. According to the findings, the
PVAT from lupus mice exhibits dysfunctional and inflamed characteristics, including
impaired endothelium-dependent relaxation of the thoracic aorta, phenotypic switching,
immune cell infiltration, and adventitial hyperplasia. The outcomes suggest the involvement
of PVAT in vascular disease in lupus, providing new insights into the pathophysiology
of cardiovascular complications in lupus and implying that targeting PVAT might be
a potential therapeutic approach in lupus.
Luo et al. comprehensively reviewed the relationship between cholesterol metabolism
and psoriasis. Psoriasis is a prevalent chronic autoinflammatory skin disease widely
recognized as a systemic inflammatory rather than a merely cutaneous disease. Their
review, entitled: “Crosstalk Between Cholesterol Metabolism and Psoriatic Inflammation”,
emphasized the strong association between cholesterol and lipid metabolism alterations
and the onset of psoriasis. They also discussed the effects of cholesterol metabolites
and cytokines on keratinocytes, immune response, and inflammation in psoriasis. This
research fills a gap in the literature by thoroughly examining the connection between
cholesterol metabolism and psoriasis, offering novel insights and promising therapeutic
targets for further investigation.
In conclusion, we believe this Research Topic has provided a timely opportunity for
researchers to showcase their work and explore the interplay between immunometabolism
and immunometabolism-associated diseases, notably autoimmune and autoinflammatory
disorders. As such, it has opened the way for innovative therapeutic approaches.
Author contributions
FZ: Writing – original draft, Writing – review & editing. GR: Writing – review & editing.
SL: Writing – review & editing. QC: Writing – review & editing.