A murine model for human immune thrombocytopenic purpura and comparative analysis of multiple gene expression in bone marrow and spleen

Homeostasis of platelet number in human and other mammals is well maintained for prevention of minor bleeding and for other im- munological functions, but the exact molecular mechanism responsible for immune thrombocytopenic purpura （ITP） has not been fully understood. In an effort to identify genetic factors involved in initiation of platelet production in response to bleeding injury or platelet destruction, we have successfully generated an animal model of human ITP via intraperitoneal injection of anti-platelet antibody into the Balb/c mouse. Platelet counts were dropped dramatically in animals that received antibody injection within 4 h, maintained at the mini- mum level for a period of 44 h, started to rebound after 48 h, and reached to the maximum at 144 h （6 days）. Final homeostasis reached at approximately 408 h （17 days）, following a minor cycle of platelet number fluctuation. Using semi-quantitative RT-PCR, we assessed and compared mRNA level of CD41, c-myb, c-mpl, caspase-3, caspase-9, GATA-1, and Bcl-xl in bone marrow and spleen. Alteration of mRNA expression was correlated with the change of platelet level, and an inverse relationship was found for expression of the genes be- tween bone marrow and spleen. No transcription was detectable for any of the seven genes in bone marrow at the time when platelet number reached the maximum （144 h）. In contrast, mRNA transcripts of the seven genes were found to be at the highest level in spleen tissue. This is the first study of simultaneous detection of multiple platelet related genes in a highly reproducible ITP animal model. Our results provided the supportive evidence that expression of the above seven genes are more related to negative regulation of platelet number in spleen tissue, at least in the model animals.

Immune thrombocytopenic purpura induced by intestinal tuberculosis in a liver transplant recipient

A variety of clinical manifestations are associated directly or indirectly with tuberculosis. Among them, haematological abnormalities can be found in both the pulmonary and extrapulmonary forms of the disease. We report a case of immune thrombocytopenic purpura(ITP) associated with intestinal tuberculosis in a liver transplant recipient. The initial management of thrombocytopenia, with steroids and intravenous immunoglobulin, was not successful, and the lack oftuberculosis symptoms hampered a proper diagnostic evaluation. After the diagnosis of intestinal tuberculosis and the initiation of specific treatment, a progressive increase in the platelet count was observed. The mechanism of ITP associated with tuberculosis has not yet been well elucidated, but this condition should be considered in cases of ITP that are unresponsive to steroids and intravenous immunoglobulin, especially in immunocompromised patients and those from endemic areas.

Study of establishing disease-syndrome combined with animal model for immune thrombocytopenic purpura without additional conditions

Objective:To explore the feasibility of establishing the disease-syndrome combined animal model for immune thrombocytopenic purpura(ITP)without additional conditions.Methods:Three batches of data related to the ITP model mice obtained by replication at different time were analyzed,and whether the APS-injected model mice replicated through the passive immune modeling method could simulate the pathogenesis and clinical characteristics of human ITP was evaluated according to the differentiation criteria for diseasesyndrome combined model.Results:The APS-injected replicated ITP model mice possessed the following traits:(1)Compared with the normal group,the platelet count was significantly decreased,and coagulation time was significantly increased in the model group(P<.01).(2)Compared with the normal group,the medullary thrombocytogenous megakaryocytes were significantly decreased(P<.05,.01,.001).(3)The APS-injected sites and other parts of the model mice had spontaneous hemorrhage.(4)Behavioral changing signs were observed 1 week after the modeling(i.e.low activity,delayed activity,poor appetite,skin petechia/hemorrhage and spontaneous hemorrhage at the injected sites or other parts),and were getting more and more severe.Conclusion:According to the syndrome differentiation criteria for disease-syndrome combined model of ITP,the APS-injected animal model of ITP replicated through the passive immune modeling method without additional conditions possesses the characteristics of disease-syndrome combined model.It provides an ideal tool for the development of traditional Chinese medicine pharmacology experiment.

Eltrombopag Managed Severe Immune Thrombocytopenic Purpura in Pregnancy: A Case Report, Latifa Hospital, DHA, Dubai, UAE

Immune thrombocytopenic purpura (ITP) is an acquired autoimmune disorder, defined by a platelet count of less than 100 × 109/L, secondary to impaired production and immune destruction of platelets. Bleeding tendency is the main presentation of this condition. Clinical symptoms and investigations will confirm the diagnosis. Steroid is the first line of treatment. Although Rituximab and Thrombopoietin receptor agonists are useful second line agents in non-pregnant adults, the data about their role in pregnancy are still limited. We present the case of a 30 year old primigravida, who was a known case of chronic ITP since childhood;the course of her disease was fluctuating, for which oral steroids were used accordingly. She presented with gum bleeding and petechial rash with very low platelets count. She was sponsored by the Patient Support Program and was given Eltrombopag during the third trimester. She responded well to Eltrombopag with no noticeable side effects, neither to the mother nor to the baby so far. Eltrombopag has been assigned Category C by the Federal Drugs Agency (FDA) nevertheless there are no well controlled data in the literature about its role in pregnancy.

Chronic Immune Thrombocytopenic Purpura in a Young Female with Rheumatoid Arthritis (Unusual Course)

We present a case of a 29-year-old female from Sudan, who was diagnosed with rheumatoid arthritis (RA) in 2005 and with immune thrombocytopenic purpura (ITP) in 2009. The ITP immediately followed using, for four weeks, a combination of medications that included rifampicin. The platelets count continued to be low thereafter. During the year following her diagnosis with ITP, she reported gradual improvement in her joints symptoms, which continued during her pregnancy in 2011. Following puerperium, her chronic ITP resolved completely;however, her joint disease flared up few months later. To our knowledge, there are no reported cases of chronic ITP, which were drug induced at first in a patient of RA except with gold therapy. Similarly, there are no reports on cases that recovered from chronic ITP after delivery. Finally, this case highlights the impact different coexisting autoimmune diseases may have on each other regarding course and prognosis.

Helicobacter pylori eradication in patients with chronic immune thrombocytopenic purpura

AIM:To assess the effect of Helicobacter pylori(H.pylori)eradication on platelet counts in patients with chronic immune thrombocytopenic purpura(cITP).METHODS:A total of 36 cITP patients were included in the study.The diagnosis of H.pylori was done by rapid urease test and Giemsa staining of the gastric biopsy specimen.All H.pylori positive patients received standard triple therapy for 14 d and were subjected for repeat endoscopy at 6 wk.Patients who continued to be positive for H.pylori on second endoscopyreceived second line salvage therapy.All the patients were assessed for platelet response at 6 wk,3rd and 6th months.RESULTS:Of the 36 patients,17 were positive for H.pylori infection and eradication was achieved in16 patients.The mean baseline platelet count in the eradicated patients was 88615.38±30117.93/mm3and platelet count after eradication at 6 wk,3 mo and6 mo was 143230.77±52437.51/mm3(P=0.003),152562.50±52892.3/mm3(P=0.0001),150187.50±41796.68/mm3(P=0.0001)respectively and in the negative patients,the mean baseline count was71000.00±33216.46/mm3 and at 6 wk,3rd and 6th month follow up was 137631.58±74364.13/mm3(P=0.001),125578.95±71472.1/mm3(P=0.005),77210.53±56892.28/mm3(P=0.684)respectively.CONCLUSION:Eradication of H.pylori leads to increase in platelet counts in patients with cITP and can be recommended as a complementary treatment with conventional therapy.

General Anesthesia for Cesarean Section in a Pregnant Woman with Immune Thrombocytopenic Purpura (ITP): A Case Report and Review of the Literature

Background: Management of immune thrombocytopenia (ITP) during pre- gnancy can be challenging, particularly by identifying a threshold for safe administration of neuraxial/general anesthesia and minimizing postpartum hemorrhage. There is controversy over the safety of cesarean section (CS) in ITP patients. In this case report, we discuss general anesthesia management in a patient with ITP with severe thrombocytopenia. Case Presentation: A 28-year-old female with relapsed/refractory ITP and severe thrombocytopenia underwent general anesthesia and emergent cesarean section with successful outcomes and minimal bleeding. Platelet counts before CS were 5000 × 109 L, the patient received 1 unit of platelets before the procedure and 1 unit of platelet and tranexamic acid 500 mg was injected slowly during the procedure. No evidence of bleeding and no complications were observed in the patient or newborn. Conclusions: In an emergent circumstance, general anesthesia and cesarean section procedure were performed safely in a patient with severe thrombocytopenia, no hemorrhagic complications were seen for this patient or neonate. Objective of This Manuscript: To share our experience of a safe emergent CS procedure and general anesthesia in a patient with severe thrombocytopenia. Our experience may guide the management of ITP patients in emergent delivery circumstances.

Immune checkpoint inhibitor-associated gastritis:Patterns and management

Immune checkpoint inhibitors(ICIs)are widely used due to their effectiveness in treating various tumors.Immune-related adverse events(irAEs)are defined as adverse effects resulting from ICI treatment.Gastrointestinal irAEs are a common type of irAEs characterized by intestinal side effects,such as diarrhea and colitis,which may lead to the cessation of ICIs.Although irAE gastritis is rarely reported,it may lead to serious complications such as gastrorrhagia.Furthermore,irAE gastritis is often difficult to identify early due to its diverse symptoms.Although steroid hormones and immunosuppressants are commonly used to reverse irAEs,the best regimen and dosage for irAE gastritis remains uncertain.In addition,the risk of recurrence of irAE gastritis after the reuse of ICIs should be considered.In this editorial,strategies such as early identification,pathological diagnosis,mana-gement interventions,and immunotherapy rechallenge are discussed to enable clinicians to better manage irAE gastritis and improve the prognosis of these patients.

A case of adverse reactions of immune thrombocytopenic purpura caused by poliovirus vaccine

The child patient, male, 4 months and 16 days old, was vaccinated orally by Type I Type III Live Attenuated Oral Poliomyelitis Vaccine (human diploid cells) at 10:45 a.m. on June 1st of 2016 in Shaoxian Community Health Service Center of our hospital. Two hours after vaccination, the child patient showed erythema scattered on the upper of the left knee, on the right calf and on the abdomen. The forearm of the left upper limb was scattered with punctate rashes. He was admitted to Department of Pediatrics of our hospital at 12:32 on June 1st of 2016. The diagnosis was 'immune thrombocytopenic purpura'. After admission, the child patient received expert consultation and systematic treatment, consequently getting better.

Involvement of Autoimmune Diseases in the Pathogenesis of Chronic Immune Thrombocytopenic Purpura

Chronic immune thrombocytopenic purpura (ITP) is a condition based on an immune-mediated mechanism that determines the premature hyperdestruction of the thrombocytes in peripheral blood, as well as their deficient synthesis at the level of the bone marrow. The chronic immune purpura could be of primary, idiopathic cause, as well as of secondary cause, occurring in the context of other pathologies. The characteristic of the primary form of the disease is the presence of isolated thrombocytopenia, defined by a platelet count under 100,000/mm3 in peripheral blood, in the absence of supporting causes for thrombocytopenia. In the secondary form of the disease, the decreased platelet count is due to associated pathologies involving an immune mechanism, responsible for the occurrence of thrombocytopenia. This study aims to emphasize the involvement of autoimmune diseases, such as systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid polyarthritis or antiphospholipid syndrome in the pathogenesis of secondary thrombocytopenia. Furthermore, the study was conducted on a sample of 40 patients, divided into two groups: The first group comprising asymptomatic patients diagnosed with thrombocytopenia following routine tests, and the second group comprising patients with hemorrhagiparous symptomatology (petechiae, ecchymoses, epistaxis, gingivorrhagia), who went to the doctor in order to determine the etiology of the hemorrhagiparous syndrome. The average value of the thrombocytopenia of the patients included in the study was of 60.20 ± 19.75 × 103/μL. Laboratory investigations performed in order to establish the etiology of thrombocytopenia showed that 80% of patients presented positive antiplatelet antibodies. Moreover, 20% of the patients in the study showed positive anti-double-stranded DNA, 20% were identified with IgG anticardiolipin antibodies, while antinuclear antibodies were present in 10% of the patients.

DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

The early life immune dynamics and cellular drivers at single-cell resolution in lamb forestomachs and abomasum

Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants,especially the immune development.However,the dynamics of immune development are poorly understood.Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep,at 5,10,15,and 25 days of age.We found that forestomachs share similar gene expression patterns,all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25,whereas the metabolic function were significantly downregulated with age.We constructed a cell landscape of the four-chambered stomach using single-cell sequencing.Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells,monocytes and macrophages,as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues.Moreover,the non-immune cells such as epithelial cells play key roles in immune maturation.Cell communication analysis predicted that in addition to immune cells,non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs.Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life.We also identified the gene expression patterns and functional cells associated with immune development.Additionally,we identified some key receptors and signaling involved in immune regulation.These results help to understand the early life immune development at single-cell resolution,which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.

A Prognostic Biomarker for Bladder Cancer Correlated with Immune Infiltration Is PAEP

Background: A major cause of cancer death worldwide is bladder cancer, which is the most common malignant tumor of the urinary tract. PAEP is a member of the kernel lipocalin superfamily whose members share relatively low sequence similarity but have highly conserved exon/intron structure and three-dimensional protein folding. Most lipocalins are clustered on the long arm of chromosome 9. The purpose of this study was to clarify the correlation between PAEP expression level and bladder cancer. Methods: In the TCGA database, we obtained clinical and RNA sequencing data of 431 BLCA patients, including 412 BLCA tissues and 19 normal bladder tissues in the study. Analyses of bioinformatics were conducted in this study to determine the role of PAEP in bladder cancer. A quantitative real-time PCR method was used to quantitate the gene expression profile. Additionally, the effect of PAEP on tumor immune infiltration and prognosis was analyzed. Results: PAEP was a poor prognostic biomarker of bladder cancer because it was significantly upregulated. bladder cancer patients with higher PAEP expression had poor outcomes. An AUC of 0.780 was calculated from the area under the ROC curve. PAEP was associated with T stage, pathologic stage, Histologic grade and Subtype of bladder cancer patients, and served as an independent predictor of overall survival in bladder cancer patients. Functional enrichment analysis revealed PAEP was obviously enriched in pathways connected with carcinogenesis and immunosuppression. The expression of PAEP was significantly associated with tumor immune cells and immune checkpoints according to ssGSEA and Spearman correlation analysis. Conclusions: In this study, we screened and detected a mRNA, PAEP is a prognostic and immune-related biomarker in BLCA, which may contribute to the early diagnosis and treatment of BLCA.

Hepatocellular carcinoma immune microenvironment and check point inhibitors-current status

Hepatocellular carcinoma(HCC)is the most common primary tumor of the liver and has a high mortality rate.The Barcelona Clinic Liver Cancer staging system in addition to tumor staging also links the modality of treatment available to a particular stage.The recent description of the tumor microenvironment(TME)in HCC has provided a new concept of immunogenicity within the HCC.Virusrelated HCC has been shown to be more immunogenic with higher expression of cytotoxic T lymphocytes and decreased elements for immunosuppression such as regulatory T cells.This immunogenic milieu provides a better response to immunotherapy especially immune checkpoint inhibitors(ICIs).In addition,the recent data on combining locoregional therapies and other strategies may convert the less immunogenic state of the TME towards higher immunogenicity.Therefore,data are emerging on the use of combinations of locoregional therapy and ICIs in unresectable or advanced HCC and has shown better survival outcomes in this difficult population.

Human herpesvirus 7 meningitis in an adolescent with normal immune function:A case report

BACKGROUND Human herpesvirus type 7(HHV-7)is a less common herpes virus that usually causes mild,self-limiting illnesses.However,in recent years,there have been increasing reports of HHV-7 causing serious central nervous system infections,especially meningitis.The pathogenesis and clinical features of HHV-7 meningitis,particularly in adolescents with normal immune function,remain incompletely studied.Therefore,the purpose of this report is to share a case of HHV-7 meningitis in an immunocompetent adolescent with a view to deepening our understanding of the disease.CASE SUMMARY A 12-year-old female was admitted with fever,headache,and vomiting.4 d before admission,the patient developed a fever without obvious induction,with a temperature up to 39.5℃,no convulsions,accompanied by chills,headaches,fatigue,and no muscle aches.The patient was treated with fever reduction,which could be reduced to 38℃;repeated high fever,accompanied by vomiting 7-8 times;and no abdominal pain or diarrhea.The patient was diagnosed with"acute suppurative tonsillitis"in a local hospital,and the blood routine was generally normal.The patient was given symptomatic support treatment such as"ceftriaxone sodium"and antiemetic rehydration for 2 d,and his condition did not improve.The patient's physical examination showed pharyngeal congestion,bilateral tonsil grade I hypertrophy,regression of purulent secretions,and cervical resistance.Ocular B-ultrasound:Opacity of the vitreous body and edema of the optic disc in both eyes.Optical coherence tomography examination showed that the macular fovea was generally normal in both eyes,with edema of the optic disc.DNA virus monitoring results:HHV-7.We gave ganciclovir antiviral therapy,dexamethasone anti-inflammatory treatment,mannitol to reduce cranial pressure,omeprazole to protect gastrointestinal mucosa,and calcium and potassium supplementation.CONCLUSION This study reports a case of HHV-7 meningitis in an adolescent with normal immune function.Through comprehensive analysis of the clinical manifestations,laboratory tests,and treatment methods of the patient,it is found that early identification and antiviral treatment are essential for the outcome of the disease.This case suggests that despite normal immune function,adolescents may still suffer from herpes virus type 7 meningitis,so clinicians should be vigilant and take effective treatment measures in time.

Application of immune checkpoint inhibitors and microsatellite instability in gastric cancer

In this editorial we comment on the article by Li published in the recent issue of the World Journal of Gastroenterology.We focus specifically on the application of immune checkpoint inhibitors(ICIs)and microsatellite instability(MSI)in gastric cancer(GC).The four pillars of GC management have long been considered,including surgery,chemotherapy,radiotherapy and targeted therapy.However,immunotherapy has recently emerged as a“fifth pillar”,and its use is rapidly expanding.There are four principal strategies for tumor immunotherapy:ICIs,tumor vaccines,adoptive immunotherapy and nonspecific immunomodulators.Of them,ICIs are the most advanced and widespread type of cancer immunotherapy for GC.Recent breakthrough results for ICIs have paved the way to a new era of cancer immunotherapy.In particular,inhibition of the PD-1/PD-L1 axis with ICIs,including nivolumab and pembrolizumab,has emerged as a novel treatment strategy for advanced GC.Unfortunately,these therapies are sometimes associated with often subtle,potentially fatal immune-related adverse events(irAEs),including dermatitis,diarrhea,colitis,endocrinopathy,hepatotoxicity,neuropathy and pneumonitis.We must be aware of these irAEs and improve the detection of these processes to prevent inappropriate discharges,emergency department revisits,and downstream complications.Recent studies have revealed that MSI-high or mismatch-repair-deficient tumors,regardless of their primary site,have a promising response to ICIs.So,it is important to detect MSI before applying ICIs for treatment of GC.

Autoimmune hepatitis and primary sclerosing cholangitis after direct-acting antiviral treatment for hepatitis C virus:A case report

BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV treatment,achieving a high sustained virological response(SVR)with minimal adverse events.CASE SUMMARY A 74-year-old woman with chronic HCV infection was treated with the DAAs ledipasvir,and sofosbuvir for 12 wk and achieved SVR.Twenty-four weeks after treatment completion,the liver enzyme and serum IgG levels increased,and antinuclear antibody became positive without HCV viremia,suggesting the development of autoimmune hepatitis(AIH).After liver biopsy indicated AIH,a definite AIH diagnosis was made and prednisolone was initiated.The treatment was effective,and the liver enzyme and serum IgG levels normalized.However,multiple strictures of the intrahepatic and extrahepatic bile ducts with dilatation of the peripheral bile ducts appeared on magnetic resonance cholangiopancreatography after 3 years of achieving SVR,which were consistent with primary sclerosing cholangitis.CONCLUSION The potential risk of developing autoimmune liver diseases after DAA treatment should be considered.

Helicobacter pylori infection in patients with autoimmune thrombocytopenic purpura

AIM: To compare the prevalence of Helicobacter pylori(Hpylori) infection in autoimmune thrombocytopenic purpura (AITP) patients with that of nonthrombocytopenic controls,and to evaluate the efficacy of the treatment in Hpylori(+)and Hpylori(-) AITP patients.METHODS: The prevalence of gastric Hpyloriinfection in 38 adult AITP patients (29 female and 9 male; median age 27 years; range 18-39 years) who consecutively admitted to our clinic was investagated.RESULTS: Hpyloriinfection was found in 26 of 38 AITP patients (68.5%). Hpyloriinfection was found in 15 of 23 control subjects (65.2%). The difference in Hpyloriinfection between the 2 groups was not significant. Thrombocyte count of Hpylori-positive AITP patients was significantly lower than that of Hpylori-negative AITP patients (P＜0.05).Thrombocyte recovery of Hpylori-positive group was less than that of Hpylori-negative group (P＜0.05).CONCLUSION: Hpyloriinfection should be considerecd in the treatment of AITP patients with Hpyloriinfection.

Immune regulation of the gut-brain axis and lung-brain axis involved in ischemic stroke

Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks.Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability.In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other.Here,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis.We found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic stroke.This review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.

Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.