To Explore The Peripheral Blood Immune Cell Atlas And Cell Communication Of Rheumatoid Arthritis Patients Based On Single-cell Transcriptome Sequencing

Rheumatoid arthritis(RA)is a systemic autoimmune disease caused by a combination of antigen-mediated,environmental,and genetic factors that manifests primarily as chronic inflammation of joint tissues and destruction of articular cartilage and bone tissue.RA has a complex etiology,a wide range of symptoms,and unknown mechanisms.There are no clear diagnostic criteria for RA.There is no cure,only relief of clinical symptoms,and the disease often affects extra-articular organs such as the heart,lungs and kidneys,resulting in a very high rate of disability that greatly reduces patients’ quality of life.It can take several years from the onset of the characteristic factors of RA to the appearance of clinical symptoms.Once the disease has progressed to the stage of initiation of an immune response against target organs or phenotypic expansion against endogenous antigens,the disease has reached an irreversible stage,and clinical treatment is very difficult.Peripheral blood mononuclear cells(PBMCs)are a major component of the immune system,involved in the intrinsic or adaptive immune response and are important immune cells that initiate the autoimmune inflammatory process.A systematic and complete understanding of the peripheral immune system response mechanism can better elucidate the pathogenesis of RA,but the peripheral immune mechanism of RA remains unclear.In this study,we used PBMCs from RA patients and healthy individuals to map the peripheral blood immune system landscape,characterize the cell abundance,gene expression profile,and functional changes,explore the communication patterns among PBMCs,and screen for the identification of cell subpopulations and key genes in the disease process using single-cell transcriptome sequencing technology.The specific findings of the study are as follows.1.A single-cell atlas of PBMCs in Ctrl-RA was successfully constructed,and a total of 17 major cell populations were identified,with no significant changes in the proportions of the major cell populations,but significant functional changes.2.Peripheral blood T cells from RA patients underwent metabolic defects and dysfunction,mainly manifested by suppression of processes such as antigen processing and presentation mediated by MHC class I molecules and energy metabolism.In addition,DNT cells proliferate abnormally,metabolic defects and dysfunction are evident,and signaling pathways that promote the development of inflammation are significantly activated.3.The expression of CREM,SOCS3,RSRP1,B2 M,MTFP1,and YWHAB was specifically downregulated in DNT cells from RA patients,among which,YWHAB,SOCS3,B2 M,and CREM played important regulatory roles,and could be used as potential therapeutic targets.4.Analysis of cellular communication patterns revealed a significant reduction in the number and strength of PBMCs interactions in RA patients,with 15 upregulated ligand-receptor pairs and 68 downregulated signaling ligand-receptor pairs involved in the RA process through relevant pathways.5.Several chemokines of the CC family and the CXC family(including the classical inflammatory chemokines CCL2 and CCL3)as well as pro-inflammatory cytokines(TNF,IL-1β)are highly expressed in the peripheral blood of RA patients.Through a comprehensive comparative analysis with cellular communication in synovial tissues,it was proposed for the first time that classic monocytes in peripheral blood migrate to inflammatory sites in synovial tissues under the chemotactic effect of chemokines CCL3 and CCL3L1,differentiate into macrophages,and simultaneously release pro-inflammatory cytokines such as IL-1β and TNF to participate in the inflammatory response,thus promoting the development of RA.In summary,this study systematically mapped the peripheral blood immune cells in RA,elucidated the cellular communication patterns of PBMCs,revealed that DNT cells and classic monocytes play key roles in the RA process,and screened a series of potential candidate target genes.In conclusion,these results provide a theoretical basis for further elucidating the pathogenesis of RA and exploring new therapeutic targets,and identifying early diagnostic markers for RA.