Impact of gluten intake on clinical outcomes in patients with chronic inflammatory diseases initiating biologics: Secondary analysis of the prospective multicentre BELIEVE cohort study.

Chronic inflammatory diseases (CIDs) pose a growing healthcare challenge, with a substantial proportion of patients showing inadequate response to biological treatment. There is renewed interest in dietary changes to optimize treatment regimens, with a growing body of evidence suggesting beneficial effects with adherence to a gluten-free diet. This study compared the likelihood of achieving clinical response to biological treatment after 14-16 weeks in patients with CID with high versus low-to-medium gluten intake. Secondary outcomes of interest included changes in disease activity, health-related quality of life and C-reactive protein. The study was a multicentre prospective cohort of 193 participants with a CID diagnosis (i.e. Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis, Axial Spondyloarthritis, Psoriatic Arthritis or Psoriasis) who initiated biological treatment between 2017 and 2020. Participants were stratified based on their habitual gluten intake: the upper 33.3% (high gluten intake) and the remaining 66.6% (low-to-medium gluten intake). The proportion of patients achieving clinical response to biological treatment after 14-16 weeks was compared using logistic regression models. The median gluten intake differed significantly between groups (12.5 g/day vs. 5.9 g/day, standardized mean difference = 1.399). In total, 108 (56%) achieved clinical response to treatment, with no difference between 35 (55%) in the high gluten group and 73 (57%) in the medium-to-low gluten group (OR = 0.96 [0.51-1.79], p = 0.897). No differences were found with secondary outcomes. In conclusion, this study found no association between gluten intake and response to biological treatment in patients with CID.

Deconstructing inflammatory memory across tissue setpoints using cell circuit motifs.

Tissue ecosystems are cellular communities that maintain setpoints through a network of intercellular interactions. We position health and chronic inflammatory disease as alternative stable setpoints that are: (1) robust to perturbation, and (2) capable of adaptation and memory. Inflammatory memory-the storage of prior experience to durably influence future responsiveness-is central to how tissue ecosystems may be pushed past tipping points that stabilize disease over health. Here, we develop a reductionist framework of circuit motifs that recur in tissue setpoints. In type 2 immunity, we distinctly find the emergence of two-cell positive feedback motifs. By contrast, directional motif relays and three-cell networks feature more prominently in type 1 and 17 responses. We propose that these differences guide the ecological networks established after surpassing tipping points and associate closely with therapeutic responsiveness. We highlight opportunities to improve our current knowledge of how circuit motifs interact when building towards tissue-level networks across adaptation and memory. By developing new tools for circuit motif nomination and applying them to temporal profiling of tissue ecosystems, we hope to dissect the stability of the chronic inflammatory setpoint and open therapeutic avenues for rewriting memory to restore health.

New and emerging oral therapies for psoriasis.

Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the global population. Traditional systemic treatments, such as methotrexate, cyclosporine, acitretin and fumaric acid esters, have limited efficacy and are associated with significant adverse effects, necessitating regular monitoring and posing risks of long-term toxicity. Recent advancements have introduced biologic drugs that offer improved efficacy and safety profiles. However, their high cost and the inconvenience of parenteral administration limit their accessibility. Consequently, there is a growing interest in developing new, targeted oral therapies. Small molecules, such as phosphodiesterase 4 inhibitors (e.g. apremilast) and TYK2 inhibitor (e.g. deucravacitinib), have shown promising results with favourable safety profiles. Additionally, other novel oral agents targeting specific pathways, including IL-17, IL-23, TNF, S1PR1 and A3AR, are under investigation. These treatments aim to combine the efficacy of biologics with the convenience and accessibility of oral administration, addressing the limitations of current therapies. This narrative review synthesizes the emerging oral therapeutic agents for psoriasis, focusing on their mechanisms of action, stages of development and clinical trial results.

Effects of smoking on clinical treatment outcomes amongst patients with chronic inflammatory diseases initiating biologics: secondary analyses of the prospective BELIEVE cohort study.

The prevalence and disease burden of chronic inflammatory diseases (CIDs) are predicted to rise. Patients are commonly treated with biological agents, but the individual treatment responses vary, warranting further research into optimizing treatment strategies. This study aimed to compare the clinical treatment responses in patients with CIDs initiating biologic therapy based on smoking status, a notorious risk factor in CIDs. In this multicentre cohort study including 233 patients with a diagnosis of Crohn's disease, ulcerative colitis, rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis or psoriasis initiating biologic therapy, we compared treatment response rates after 14 to 16 weeks and secondary outcomes between smokers and non-smokers. We evaluated the contrast between groups using logistic regression models: (i) a "crude" model, only adjusted for the CID type, and (ii) an adjusted model (including sex and age). Among the 205 patients eligible for this study, 53 (26%) were smokers. The treatment response rate among smokers (n = 23 [43%]) was lower compared to the non-smoking CID population (n = 92 [61%]), corresponding to a "crude" OR of 0.51 (95% CI: [0.26;1.01]) while adjusting for sex and age resulted in consistent findings: 0.51 [0.26;1.02]. The contrast was apparently most prominent among the 38 RA patients, with significantly lower treatment response rates for smokers in both the "crude" and adjusted models (adjusted OR 0.13, [0.02;0.81]). Despite a significant risk of residual confounding, patients with CIDs (rheumatoid arthritis in particular) should be informed that smoking probably lowers the odds of responding sufficiently to biological therapy. Registration: Clinical.Trials.gov NCT03173144.

Clearing the Path: Exploring Apoptotic Cell Clearance in Inflammatory and Autoimmune Disorders for Therapeutic Advancements.

Inflammatory and autoimmune disorders, characterized by dysregulated immune responses leading to tissue damage and chronic inflammation, present significant health challenges. This review uniquely focuses on efferocytosis-the phagocyte-mediated clearance of apoptotic cells-and its pivotal role in these disorders. We delve into the intricate mechanisms of efferocytosis' four stages and their implications in disease pathogenesis, distinguishing our study from previous literature. Our findings highlight impaired efferocytosis in conditions like atherosclerosis and asthma, proposing its targeting as a novel therapeutic strategy. We discuss the therapeutic potential of efferocytosis in modulating immune responses and resolving inflammation, offering a new perspective in treating inflammatory disorders.

Immunometabolism in atherosclerosis: a new understanding of an old disease.

Atherosclerosis, a chronic inflammatory condition, remains a leading cause of death globally, necessitating innovative approaches to target pro-atherogenic pathways. Recent advancements in the field of immunometabolism have highlighted the crucial interplay between metabolic pathways and immune cell function in atherogenic milieus. Macrophages and T cells undergo dynamic metabolic reprogramming to meet the demands of activation and differentiation, influencing plaque progression. Furthermore, metabolic intermediates intricately regulate immune cell responses and atherosclerosis development. Understanding the metabolic control of immune responses in atherosclerosis, known as athero-immunometabolism, offers new avenues for preventive and therapeutic interventions. This review elucidates the emerging intricate interplay between metabolism and immunity in atherosclerosis, underscoring the significance of metabolic enzymes and metabolites as key regulators of disease pathogenesis and therapeutic targets.

Mapping the immune cell landscape of severe atopic dermatitis by single-cell RNA-seq.

BACKGROUND: Efforts to profile atopic dermatitis (AD) tissues have intensified, yet comprehensive analysis of systemic immune landscapes in severe AD remains crucial. METHODS: Employing single-cell RNA sequencing, we analyzed over 300,000 peripheral blood mononuclear cells from 12 severe AD patients (Eczema area and severity index (EASI) > 21) and six healthy controls. RESULTS: Results revealed significant immune cell shifts in AD patients, including increased Th2 cell abundance, reduced NK cell clusters with compromised cytotoxicity, and correlated Type 2 innate lymphoid cell proportions with disease severity. Moreover, unique monocyte clusters reflecting activated innate immunity emerged in very severe AD (EASI > 30). While overall dendritic cells (DCs) counts decreased, a distinct Th2-priming subset termed "Th2_DC" correlated strongly with disease severity, validated across skin tissue data, and flow cytometry with additional independent severe AD samples. Beyond the recognized role of Th2 adaptive immunity, our findings highlight significant innate immune cell alterations in severe AD, implicating their roles in disease pathogenesis and therapeutic potentials. CONCLUSION: Apart from the widely recognized role of Th2 adaptive immunity in AD pathogenesis, alterations in innate immune cells and impaired cytotoxic cells have also been observed in severe AD. The impact of these alterations on disease pathogenesis and the effectiveness of potential therapeutic targets requires further investigation.

Bilateral plasma cell mastitis simulating breast cancer: a case report and literature review.

Plasma cell mastitis (PCM) is a chronic inflammatory disease of the breast. It is a benign entity mainly found in nonpregnant and nonlactating women. PCM presents with symptoms of inflammation, breast erythema, masses, and indurations. We herein describe a 26-year-old woman with a 2-year history of right breast swelling and a 1-year history of left breast swelling during pregnancy and lactation. She was clinically diagnosed with bilateral breast cancer, but a biopsy specimen revealed PCM. During pregnancy and lactation, PCM can present as bilateral lesions. Early presentation and diagnosis are crucial because PCM, a benign disease, can lead to remarkable morbidity if allowed to progress to an advanced stage.

Osteopathic manipulative treatment for chronic inflammatory diseases.

Chronic inflammatory diseases (CIDs) are debilitating and potentially lethal illnesses that affect a large proportion of the global population. Osteopathic manipulative treatment (OMT) is a manual therapy technique developed and performed by osteopathic physicians that facilitates the body's innate healing processes. Therefore, OMT may prove a beneficial anti-inflammatory modality useful in the management and treatment of CIDs. This work aims to objectively evaluate the therapeutic benefits of OMT in patients with various CIDs. In this review, a structured literature search was performed. The included studies involving asthma, chronic obstructive pulmonary disease, irritable bowel syndrome, ankylosing spondylitis, and peripheral arterial disease were selected for this work. Various OMT modalities, including lymphatic, still, counterstain, and muscle energy techniques, were utilized. Control treatments included sham techniques, routine care, or no treatment. OMT utilization led to variable patient outcomes in individuals with pathologies linked to CID.

Exercise-induced ß-hydroxybutyrate promotes Treg cell differentiation to ameliorate colitis in mice.

Increasing attention is being paid to the mechanistic investigation of exercise-associated chronic inflammatory disease improvement. Ulcerative colitis (UC) is one type of chronic inflammatory bowel disease with increasing incidence and prevalence worldwide. It is known that regular moderate aerobic exercise (RMAE) reduces the incidence or risk of UC, and attenuates disease progression in UC patients. However, the mechanisms of this RMAE's benefit are still under investigation. Here, we revealed that ß-hydroxybutyrate (ß-HB), a metabolite upon prolonged aerobic exercise, could contribute to RMAE preconditioning in retarding dextran sulfate sodium (DSS)-induced mouse colitis. When blocking ß-HB production, RMAE preconditioning-induced colitis amelioration was compromised, whereas supplementation of ß-HB significantly rescued impaired ß-HB production-associated defects. Meanwhile, we found that RMAE preconditioning significantly caused decreased colonic Th17/Treg ratio, which is considered to be important for colitis mitigation; and the downregulated Th17/Treg ratio was associated with ß-HB. We further demonstrated that ß-HB can directly promote the differentiation of Treg cell rather than inhibit Th17 cell generation. Furthermore, ß-HB increased forkhead box protein P3 (Foxp3) expression, the core transcriptional factor for Treg cell, by enhancing histone H3 acetylation in the promoter and conserved noncoding sequences of the Foxp3 locus. In addition, fatty acid oxidation, the key metabolic pathway required for Treg cell differentiation, was enhanced by ß-HB treatment. Lastly, administration of ß-HB without exercise significantly boosted colonic Treg cell and alleviated colitis in mice. Together, we unveiled a previously unappreciated role for exercise metabolite ß-HB in the promotion of Treg cell generation and RMAE preconditioning-associated colitis attenuation.

Long-Term Outcomes After Transcatheter Aortic Valve Implantation in Patients With Chronic Inflammatory Disease.

BACKGROUND: Chronic inflammatory disease (CID) accelerates atherosclerosis and the development of aortic stenosis. Data on long-term outcomes after transcatheter aortic valve implantation (TAVI) in those patients are missing. The aim of this study was to investigate the clinical long-term outcomes of patients with and without autoimmune-related CID undergoing TAVI for the treatment of severe aortic stenosis. METHODS AND RESULTS: From a prospective registry, consecutive patients with TAVI were included. Baseline clinic and imaging data (echocardiographic and computed tomography) were analyzed. Long-term (up to 5 years) clinical and echocardiographic outcomes were studied. Of 1000 consecutive patients (mean age 81±6 years, 46% female), 107 (11%) had CID; the most frequent entities included polymyalgia rheumatica (31%) and rheumatoid arthritis (28%). Patients with CID were predominantly female (60% versus 44%, P=0.002) and more often had pulmonary disorders (21% versus 13%, P=0.046) and atrial fibrillation (32% versus 20%, P=0.003). The presence of CID was associated with a higher rate of postinterventional infection (5% versus 1%, P=0.007) and further emerged as a risk factor for rehospitalization for bleeding or infection (hazard ratio, 1.93 and 1.62, respectively). Premature valve degeneration, endocarditis, and all-cause mortality were not increased among patients with CID. CONCLUSIONS: This real-world analysis found that patients with CID undergoing TAVI were associated with a higher risk of postinterventional infectious complications and rehospitalization due to infection. However, valve durability and survival seem not to differ between patients with TAVI with versus without CID.

Comparison of Cell-based and Nanoparticle-based Therapeutics in Treating Atherosclerosis.

Today, cardiovascular diseases are among the biggest public health threats worldwide. Atherosclerosis, a chronic inflammatory disease with complex aetiology and pathogenesis, predispose many of these conditions, including the high mortality rate-causing ischaemic heart disease and stroke. Nevertheless, despite the alarming prevalence and absolute death rate, established treatments for atherosclerosis are unsatisfactory in terms of efficacy, safety, and patient acceptance. The rapid advancement of technologies in healthcare research has paved new treatment approaches, namely cell-based and nanoparticle-based therapies, to overcome the limitations of conventional therapeutics. This paper examines the different facets of each approach, discusses their principles, strengths, and weaknesses, analyses the main targeted pathways and their contradictions, provides insights on current trends as well as highlights any unique mechanisms taken in recent years to combat the progression of atherosclerosis.

Emerging drug delivery systems with traditional routes - A roadmap to chronic inflammatory diseases.

Inflammation is prevalent and inevitable in daily life but can generally be accommodated by the immune systems. However, incapable self-healing and persistent inflammation can progress to chronic inflammation, leading to prevalent or fatal chronic diseases. This review comprehensively covers the topic of emerging drug delivery systems (DDSs) for the treatment of chronic inflammatory diseases (CIDs). First, we introduce the basic biology of the chronic inflammatory process and provide an overview of the main CIDs of the major organs. Next, up-to-date information on various DDSs and the associated strategies for ensuring targeted delivery and stimuli-responsiveness applied to CIDs are discussed extensively. The implementation of traditional routes of drug administration to maximize their therapeutic effects against CIDs is then summarized. Finally, perspectives on future DDSs against CIDs are presented.

The effect of saffron and corrective exercises on depression and quality of life in women with multiple sclerosis: A randomized controlled clinical trial.

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system which causes various complications such as reduced ability to do daily activities, depression and early death of patients. The present study aimed to compare the effect of saffron and corrective exercises on depression and quality of life in women with MS. This randomized controlled clinical trial was conducted on 80 MS women for 12 weeks. Participants were selected through convenience sampling and allocated into four study groups (three intervention groups and one control group) using the stratified block randomization. The Expanded Disability Status Scale, Beck Depression Inventory and The Multiple Sclerosis Impact Scale were used to collect data at the start of the study and also at the end of the sixth and the twelfth weeks. At the end of the twelfth week, the depression mean scores in all experimental groups (saffron group, corrective exercises group, corrective exercises + saffron group) were significantly different compared to the control group (P < 0.05), and this difference in corrective exercises + saffron group was more than the others. Also, at the end of the twelfth week, the mean scores of the quality of life (both physical and mental dimensions) in all experimental groups were significantly different from the control group (P < 0.05). The saffron group in physical dimension and the corrective exercises + saffron group in psychological dimension showed a significant difference with other groups. Although each of the corrective exercises program and saffron consumption alone were effective in reducing depression and enhancing the quality of life in MS patients, the consequences will be more beneficial in case these two interventions are used together. Therefore, it is necessary to encourage MS patients to consume saffron supplement along with doing physical activities in caring and rehabilitation programs.

Are Antimicrobial Peptides a 21st-Century Solution for Atopic Dermatitis?

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that is the result of various environmental, bacterial and genetic stimuli, which culminate in the disruption of the skin's barrier function. Characterized by highly pruritic skin lesions, xerosis and an array of comorbidities among which skin infections are the most common, this condition results in both a significant loss of quality of life and in the need for life-long treatments (e.g., corticosteroids, monoclonal antibodies and regular antibiotic intake), all of which may have harmful secondary effects. This, in conjunction with AD's rising prevalence, made the development of alternative treatment strategies the focus of both the scientific community and the pharmaceutical industry. Given their potential to both manage the skin microbiome, fight infections and even modulate the local immune response, the use of antimicrobial peptides (AMPs) from more diverse origins has become one of the most promising alternative solutions for AD management, with some being already used with some success towards this end. However, their production and use also exhibit some limitations. The current work seeks to compile the available information and provide a better understanding of the state of the art in the understanding of AMPs' true potential in addressing AD.

Design Development of the SMARTCLIC®/CLICWISE® Injection Device for Self-Administered Subcutaneous Therapies: Findings from Usability and Human Factor Studies.

INTRODUCTION: An easy-to-use, multiuse, single-patient, electromechanical autoinjector, the SMARTCLIC®/CLICWISE® injection device, was recently developed to improve the self-administration options available to patients with chronic inflammatory disease treated with biologic agents. An extensive series of studies were conducted to guide the design and development of this device and to ensure its safety and effectiveness. METHODS: Participants in two user preference studies and three formative human factor (HF) studies evaluated evolving iterations of the autoinjector device, dose dispenser cartridge, graphical user interface, and informational materials; participants in a summative HF test subsequently assessed the final proposed commercially representative product. In the user preference studies, rheumatologists and patients with chronic inflammatory disease, interviewed online and in-person, provided feedback on the design and functionality of four prototypes. In the HF studies, the safety, effectiveness, and usability of adapted prototypes were assessed under simulated-use conditions by patients with chronic inflammatory disease, caregivers, and healthcare professionals (HCPs). The safety and effectiveness of the final refined device and system were confirmed in a summative HF test by patients and HCPs in simulated-use scenarios. RESULTS: Rheumatologists (n = 204) and patients (n = 39) interviewed in the two user preference studies provided feedback on the device size, feature ergonomics, and usability that guided prototype development in the subsequent formative HF studies. Observations from patients, caregivers, and HCPs (n = 55) participating in the latter studies yielded additional critical design revisions that culminated in development of the final device and system. Of 106 injection simulations conducted in the summative HF test, all resulted in successful medication delivery, and no potential harms were associated with injection-related use events. CONCLUSION: Findings from this research facilitated development of the SmartClic/ClicWise autoinjector device and demonstrated that it could be used safely and effectively by participants representative of the intended-use population of patients, lay caregivers, and HCPs.

Canthin-6-Ones: Potential Drugs for Chronic Inflammatory Diseases by Targeting Multiple Inflammatory Mediators.

Chronic inflammatory disease (CID) is a category of medical conditions that causes recurrent inflammatory attacks in multiple tissues. The occurrence of CID is related to inappropriate immune responses to normal tissue substances and invading microbes due to many factors, such as defects in the immune system and imbalanced regulation of commensal microbes. Thus, effectively keeping the immune-associated cells and their products in check and inhibiting aberrant activation of the immune system is a key strategy for the management of CID. Canthin-6-ones are a subclass of ß-carboline alkaloids isolated from a wide range of species. Several emerging studies based on in vitro and in vivo experiments reveal that canthin-6-ones may have potential therapeutic effects on many inflammatory diseases. However, no study has yet summarized the anti-inflammatory functions and the underlying mechanisms of this class of compounds. This review provides an overview of these studies, focusing on the disease entities and the inflammatory mediators that have been shown to be affected by canthin-6-ones. In particular, the major signaling pathways affected by canthin-6-ones, such as the NLR family pyrin domain containing 3 (NLRP3) inflammasome and the NF-κB signaling pathway, and their roles in several CIDs are discussed. Moreover, we discuss the limitations in studies of canthin-6-ones and provide possible solutions. In addition, a perspective that may suggest possible future research directions is provided. This work may be helpful for further mechanistic studies and possible therapeutic applications of canthin-6-ones in the treatment of CID.

Smoking Suppresses the Therapeutic Potential of Adipose Stem Cells in Crohn's Disease Patients through Epigenetic Changes.

Patients with Crohn's disease (CD) who smoke are known to have a worse prognosis than never-smokers and a higher risk for post-surgical recurrence, whereas patients who quit smoking after surgery have significantly lower post-operative recurrence. The hypothesis was that smoking induces epigenetic changes that impair the capacity of adipose stem cells (ASCs) to suppress the immune system. It was also questioned whether this impairment remains in ex-smokers with CD. ASCs were isolated from non-smokers, smokers and ex-smokers with CD and their interactions with immune cells were studied. The ASCs from both smokers and ex-smokers promoted macrophage polarization to an M1 pro-inflammatory phenotype, were not able to inhibit T- and B-cell proliferation in vitro and enhanced the gene and protein expression of inflammatory markers including interleukin-1b. Genome-wide epigenetic analysis using two different bioinformatic approaches revealed significant changes in the methylation patterns of genes that are critical for wound healing, immune and metabolic response and p53-mediated DNA damage response in ASCs from smokers and ex-smokers with CD. In conclusion, cigarette smoking induces a pro-inflammatory epigenetic signature in ASCs that likely compromises their therapeutic potential.

Co-occurrence of Amyloid Goiter and Adipose Metaplasia in a Patient With History of Pulmonary Tuberculosis: A Case Report.

Amyloid goiter is described as an accumulation of amyloid, an amorphous proteinaceous material, in the thyroid gland. The deposition of amyloid is relatively common in the thyroid gland. However, a significant clinical enlargement due to amyloid accumulation and fat deposition in the thyroid stroma resulting in diffuse goiter leading to compressive symptoms is a rare phenomenon. In this report, we describe a rare case of amyloid goiter with adipose metaplasia in a 38-year-old woman with a history of pulmonary tuberculosis who presented to the outpatient department with complaints of heartburn, abdominal discomfort, and hoarseness of voice. Incidentally patient had diffused multinodular neck swelling. Preliminary blood investigations were normal. The contrast-enhanced computed tomography neck showed multiple non-enhancing lesions and a diffusely enlarged thyroid gland, causing a mass effect on the oropharynx posteriorly and minimally on the trachea. Fine needle aspiration cytology thyroid revealed thyroiditis. The patient underwent a total thyroidectomy, and histopathological examination of the specimen showed an extracellular eosinophilic amorphous substance that was positive for Congo red and showed apple-green birefringence under polarized light, and large areas of adipose metaplasia were noted, and a diagnosis was made. The amyloid involvement can result from localized primary deposition or secondary to chronic inflammatory disease. The prevalence of amyloid goiter in developed countries is due to primary amyloidosis, and in developing countries is due to secondary amyloidosis. Patients with a history of pulmonary tuberculosis commonly present with renal amyloidosis as its complication. Patients with an enlarged thyroid gland and a history of chronic inflammatory conditions or plasma cell dyscrasias should be evaluated with extreme suspicion. The correlation of tuberculosis with the subsequent development of amyloid goiter highlights the need for research in this area.

Single-Cell Genomics for Investigating Pathogenesis of Inflammatory Diseases.

Recent technical advances have enabled unbiased transcriptomic and epigenetic analysis of each cell, known as "single-cell analysis". Single-cell analysis has a variety of technical approaches to investigate the state of each cell, including mRNA levels (transcriptome), the immune repertoire (immune repertoire analysis), cell surface proteins (surface proteome analysis), chromatin accessibility (epigenome), and accordance with genome variants (eQTLs; expression quantitative trait loci). As an effective tool for investigating robust immune responses in coronavirus disease 2019 (COVID-19), many researchers performed single-cell analysis to capture the diverse, unbiased immune cell activation and differentiation. Despite challenges elucidating the complicated immune microenvironments of chronic inflammatory diseases using existing experimental methods, it is now possible to capture the simultaneous immune features of different cell types across inflamed tissues using various single-cell tools. In this review, we introduce patient-based and experimental mouse model research utilizing single-cell analyses in the field of chronic inflammatory diseases, as well as multi-organ atlas targeting immune cells.