Graphical abstract

Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases and a prototypic inflammatory disease, affecting the small joints of the hands and feet. Chemokines and chemokine receptors play a critical role in RA pathogenesis via immune cells recruitment. Several chemokines and chemokine receptors are abundant in the peripheral blood and in the local inflamed joints of RA. Furthermore, synthetic and biologics disease modifying anti rheumatic drugs have been reported to affect chemokines expression. Thus, many studies have focused on targeting chemokines and chemokine receptors, where some have shown positive promising results. However, most of the chemokine blockers in human trials of RA treatment displayed some failures that can be attributed to several reasons in their structures and binding affinities. Nevertheless, targeting chemokines will continue to be under development, in order to improve their therapeutic potentials in RA and other autoimmune diseases. In this review we provide an up-to-date knowledge regarding the role of chemokines and chemokine receptors in RA with an emphasis on their activities on immune cells. We also discussed the effects of drugs targeting those molecules in RA. This knowledge might provide impetus for developing new therapeutic modalities to treat this chronic disease.

Pyroptosis is a newly discovered programmed cell death with inflammasome formation. Pattern recognition receptors that identify repetitive motifs of prospective pathogens such as LPS of gram‐negative bacteria are crucial to pyroptosis. Upon stimulation by pathogen‐associated molecular patterns or damage‐associated molecular patterns, proinflammatory cytokines, mainly IL‐1 family members IL‐1β and IL‐18, are released through pyroptosis specific pore‐forming protein, gasdermin D. Even though IL‐1 family members are mainly involved in innate immunity, they can be factors in adaptive immunity. Given the importance of IL‐1 family members in health and diseases, deciphering the role of pyroptosis in the regulation of innate and adaptive immunity is of great importance, especially with the recent progress in identifying the exact mechanism of such a pathway. In this review, we will focus on how the innate inflammatory mediators can regulate the adaptive immune system and vice versa via pyroptosis.

Innate lymphoid cells (ILCs) are an emerging group of immune cells that provide the first line of defense against various pathogens as well as contributing to tissue repair and inflammation. ILCs have been classically divided into three subgroups based on their cytokine secretion and transcription factor profiles. ILC nomenclature is analogous to that of T helper cells. Group 1 ILCs composed of natural killer (NK) cells as well as IFN-γ secreting ILC1s. ILC2s have the capability to produce TH2 cytokines while ILC3s and lymphoid tissue inducer (LTis) are subsets of cells that are able to secrete IL-17 and/or IL-22. A recent subset of ILC known as ILC4 was discovered, and the cells of this subset were designated as NK17/NK1 due to their release of IL-17 and IFN-γ. In this review, we sought to explain the subclasses of ILCs and their roles as mediators of lytic enzymes and inflammation.

Objectives: To compare risk factors and clinical outcomes among COVID-19 patients with or without diabetes in the United Arab Emirates (UAE). Methods: Data of 350 COVID-19 positive patients, admitted to Al Kuwait Hospital in Dubai, UAE, from February to May 2020 was collected retrospectively, including demographic data, clinical symptoms, blood tests, as well as radiographical assessments, and clinical outcomes of COVID-19. The design of the study is a retrospective cohort study. Results: COVID-19 patients with diabetes belong to an older age group, had a higher percentage of male patients, exhibited more lymphopenia and neutrophilia, and higher ferritin levels. Additionally, patients with diabetes presented fever and shortness of breath (SOB), displayed more bilateral airspace consolidation and opacities in their chest x-ray and CT scans, compared to non-diabetics. A higher percentage of critical, ICU-admitted, and death of COVID-19 cases in the diabetic group was also reported. This was along with a concomitant increase in C-reactive protein, procalcitonin, and lactate dehydrogenase levels. Conclusions: Diabetes is considered a comorbidity as diabetic patients showed more severe COVID-19 symptoms that led to critical clinical outcomes such as ICU admission and death.

IntroductionCOVID-19 is raising with a second wave threatening many countries. Therefore, it is important to understand COVID-19 characteristics across different countries.MethodsThis is a cross-sectional descriptive study of 525 hospitalized symptomatic COVID-19 patients, from the central federal hospital in Dubai-UAE during period of March to August 2020.ResultsUAE’s COVID-19 patients were relatively young; mean (SD) of the age 49(15) years, 130 (25%) were older than 60 and 4 (<1%) were younger than 18 years old. Majority were male(47; 78%). The mean (SD) BMI was 29 (6) kg/m2. While the source of contracting COVID-19 was not known in 369 (70%) of patients, 29 (6%) reported travel to overseas-country and 127 (24%) reported contact with another COVID-19 case/s. At least one comorbidity was present in 284 (54%) of patients and 241 (46%) had none. The most common comorbidities were diabetes (177; 34%) and hypertension (166; 32%). The mean (SD) of symptoms duration was 6 (3) days. The most common symptoms at hospitalization were fever (340; 65%), cough (296; 56%), and shortness of breath (SOB) (243; 46%). Most of the laboratory values were within normal range, but (184; 35%) of patients had lymphopenia, 43 (8%) had neutrophilia, and 116 (22%) had prolong international normalized ratio (INR), and 317 (60%) had high D-dimer. Chest x ray findings of consolidation was present in 334 (64%) of patients and CT scan ground glass appearance was present in 354 (68%). Acute cardiac injury occurred in 124 (24%), acute kidney injury in 111 (21%), liver injury in 101 (19%), ARDS in 155 (30%), acidosis in 118 (22%), and septic shock in 93 (18%). Consequently, 150 (29%) required ICU admission with 103 (20%) needed mechanical ventilation.ConclusionsThe study demonstrated the special profile of COVID-19 in UAE. Patients were young with diabetes and/or hypertension and associated with severe infection as shown by various clinical and laboratory data necessitating ICU admission.

IntroductionAlthough natural killer (NK) are major cells used to treat cancer patients, recent clinical trials showed that NK92 cells can be also used for the same purpose due to their high anti-tumor activity. Here, we examined whether these cells might be inflammatory due to the release of interleukin-1β (IL-1β), and whether the anti-inflammatory molecules dimethyl fumarate (DMF), or monomethyl fumarate (MMF) impair this activity.MethodsNK92 cells were examined for the synthesis and release of IL-1β utilizing RT-PCR and ELISA assay, respectively. The expression of hydroxy-carboxylic acid receptors (HCA)1, HCA2 and HCA3 was detected by immunoblotting, flow cytometry, immunofluorescence and RT-PCR assays. The activation of caspase-1 and Gasdermin D (GSDMD) was evaluated by immunoblot assay. Pyroptosis was demonstrated by immunofluorescence imaging. Expression of DNA methyltransferases (DNMTs) mRNA was determined by whole transcriptome and immunoblot analyses.ResultsLPS-induced the release of IL-1β from NK92 cells, whereas DMF or MMF inhibited this induction. The effect of these drugs was due to inhibiting the conversion of procaspase-1 into active caspase-1. NK92 cells highly expressed GSDMD, a pyroptotic-mediated molecule. However, LPS induced the distribution of GSDMD into the cell membranes, corroborated with the presence of pyroptotic bodies, an activity that was inhibited by DMF or MMF. These molecule also inhibited the generation of GSDMD through DNMT-mediated hypermethylation of the promoter region of GSDMD gene. These results were supported by increased expression of DNMTs mRNA as determined by whole transcriptome analysis.DiscussionOur results are the first to show that NK92 cells utilize GSDMD pathway to release IL-1β. Further, DMF and MMF which were previously shown to enhance NK cell cytotoxicity, also inhibit the inflammatory effects of these cells, making them most suitable for treating cancer patients.

Multiple sclerosis (MS) is an immune-mediated and neurodegenerative disorder that results in inflammation and demyelination of the central nervous system (CNS). MS symptoms include walking difficulties, visual weakening, as well as learning and memory impairment, thus affecting the quality of the patient's life. Chemokines and chemokine receptors are expressed on the immune cells as well as the CNS resident cells. Several sets of chemokine receptors and their ligands tend to be pathogenic players in MS, including CCL2,