The Unfolded Protein Response and Its Implications for Novel Therapeutic Strategies in Inflammatory Bowel Disease.

The endoplasmic reticulum (ER) is a multifunctional organelle playing a vital role in maintaining cell homeostasis, and disruptions to its functions can have detrimental effects on cells. Dysregulated ER stress and the unfolded protein response (UPR) have been linked to various human diseases. For example, ER stress and the activation of the UPR signaling pathways in intestinal epithelial cells can either exacerbate or alleviate the severity of inflammatory bowel disease (IBD), contingent on the degree and conditions of activation. Our recent studies have shown that EPICERTIN, a recombinant variant of the cholera toxin B subunit containing an ER retention motif, can induce a protective UPR in colon epithelial cells, subsequently promoting epithelial restitution and mucosal healing in IBD models. These findings support the idea that compounds modulating UPR may be promising pharmaceutical candidates for the treatment of the disease. In this review, we summarize our current understanding of the ER stress and UPR in IBD, focusing on their roles in maintaining cell homeostasis, dysregulation, and disease pathogenesis. Additionally, we discuss therapeutic strategies that promote the cytoprotection of colon epithelial cells and reduce inflammation via pharmacological manipulation of the UPR.

Characterization and utility of two monoclonal antibodies to cholera toxin B subunit.

Cholera toxin B subunit (CTB) is a potent immunomodulator exploitable in mucosal vaccine and immunotherapeutic development. To aid in the characterization of pleiotropic biological functions of CTB and its variants, we generated a panel of anti-CTB monoclonal antibodies (mAbs). By ELISA and surface plasmon resonance, two mAbs, 7A12B3 and 9F9C7, were analyzed for their binding affinities to cholera holotoxin (CTX), CTB, and EPICERTIN: a recombinant CTB variant possessing mucosal healing activity. Both 7A12B3 and 9F9C7 bound efficiently to CTX, CTB, and EPICERTIN with equilibrium dissociation constants at low to sub-nanomolar concentrations but bound weakly, if at all, to Escherichia coli heat-labile enterotoxin B subunit. In a cyclic adenosine monophosphate assay using Caco2 human colon epithelial cells, the 7A12B3 mAb was found to be a potent inhibitor of CTX, whereas 9F9C7 had relatively weak inhibitory activity. Meanwhile, the 9F9C7 mAb effectively detected CTB and EPICERTIN bound to the surface of Caco2 cells and mouse spleen leukocytes by flow cytometry. Using 9F9C7 in immunohistochemistry, we confirmed the preferential localization of EPICERTIN in colon crypts following oral administration of the protein in mice. Collectively, these mAbs provide valuable tools to investigate the biological functions and preclinical development of CTB variants.

Experimental intoxication of Brahman (Bos indicus) heifers with Enterolobium cyclocarpum fruits.

Enterolobium cyclocarpum is a poisonous plant distributed throughout the Americas. The E. cyclocarpum fruits have high toxic potential for cattle in Colombia and the clinical signs and pathological lesions are ill-defined. To begin address this issue, twelve Brahman heifers were administered E. cyclocarpum fruits and the evolution of clinical signs were recorded. Blood was collected to establish biochemical and hematological parameters. Animals were euthanized between 4 and 15 days after the initial dose was given, and tissue samples were routinely processed and stained by Hematoxylin-Eosin. The severity of clinical signs and tissue lesions were correlated with the dose of E. cyclocarpum fruits. Clinical signs included fever, tachypnea, sialorrhea, jaundice, tympanism, and diarrhea. Skin lesions were consistent with photosensitization. Hematological and biochemical tests showed increased hematocrit, neutropenia, increased serum fibrinogen, elevated hepatic enzymes and azotemia. Histology revealed panlobular cytoplasmic vacuolization and extensive foci of necrosis in the liver. The skin, fore-stomach, abomasum and intestine revealed microcirculatory, inflammatory and ulcerative changes. Protein casts and tubular epithelium vacuolization were found in kidney. Depending on the toxicosis intensity, it is concluded that E. cyclocarpum fruits may cause two clinical and pathological forms of poisoning in Brahman heifers. First, a severe intoxication at repeated exposition with high (20 g/kg/d) or low (10 g/kg/d) dose that affected the digestive and tegumentary systems and the kidney. Second, a mild to moderate form with a single low dose (10 g/kg/d) that affected in lower grades the same systems/organs.

Impact of glycoengineering and antidrug antibodies on the anticancer activity of a plant-made lectin-Fc fusion protein.

Plants are an efficient production platform for manufacturing glycoengineered monoclonal antibodies and antibody-like molecules. Avaren-Fc (AvFc) is a lectin-Fc fusion protein or lectibody produced in Nicotiana benthamiana, which selectively recognizes cancer-associated high-mannose glycans. In this study, we report the generation of a glycovariant of AvFc that is devoid of plant glycans, including the core α1,3-fucose and ß1,2-xylose residues. The successful removal of these glycans was confirmed by glycan analysis using HPLC. This variant, AvFcΔXF , has significantly higher affinity for Fc gamma receptors and induces higher levels of luciferase expression in an antibody-dependent cell-mediated cytotoxicity (ADCC) reporter assay against B16F10 murine melanoma cells without inducing apoptosis or inhibiting proliferation. In the B16F10 flank tumour mouse model, we found that systemic administration of AvFcΔXF , but not an aglycosylated AvFc variant lacking affinity for Fc receptors, significantly delayed the growth of tumours, suggesting that Fc-mediated effector functions were integral. AvFcΔXF treatment also significantly reduced lung metastasis of B16F10 upon intravenous challenge whereas a sugar-binding-deficient mutant failed to show efficacy. Lastly, we determined the impact of antidrug antibodies (ADAs) on drug activity in vivo by pretreating animals with AvFcΔXF before implanting tumours. Despite a significant ADA response induced by the pretreatment, we found that the activity of AvFcΔXF was unaffected by the presence of these antibodies. These results demonstrate that glycoengineering is a powerful strategy to enhance AvFc's antitumor activity.

Prevalence and Molecular Characterization of Salmonella Isolated from Broiler Farms at the Tolima Region-Colombia.

Salmonella is an important animal and human pathogen responsible for Salmonellosis, and it is frequently associated with the consumption of contaminated poultry products. The aim of this study was to estimate the prevalence of Salmonella in the poultry farms and to determine the genetic relationship. A total of 135 samples collected from fifteen broiler farms, including cloacal, feed, water, environmental and farm operator faeces samples were subjected to microbiological isolation. Molecular confirmation of Salmonella isolates was carried out by amplification of the invA gene, discrimination of d-tartrate-fermenting Salmonella isolates using multiplex PCR, and subsequently analysed by pulsed-field gel electrophoresis (PFGE). A survey questionnaire was conducted to identify potential risk factors for Salmonella presence in broiler farms. The prevalence of Salmonella at the farm level was 26.67%, and Salmonella isolates were serotyped as S. Paratyphi B and all isolates were d-tartrate-fermenting (dT+). PFGE showed three highly similar clusters and one significantly different Salmonella isolate. S. Paratyphi B continued to be present in different links of the poultry chain in the Tolima region, and identification of its main source is necessary to control its dissemination.

A common Salmonella Enteritidis sequence type from poultry and human gastroenteritis in Ibagué, Colombia / Un tipo de secuencia común de Salmonella Enteritidis de origen aviar y de humano con gastroenteritis en Ibagué, Colombia

Abstract Introduction: Salmonella Enteritidis is a major cause of human salmonellosis in the world, with contaminated eggs and raw chicken meat as the main routes of infection. The main Salmonella spp. serovars circulating in laying hen farms, the surface of eggs, and in raw chicken carcasses have been identified in Ibagué, Colombia. However, it is unknown whether those serovars are responsible for human gastroenteritis. Objective: To evaluate the genetic relationship between gastroenteritis and Salmonella Enteritidis isolates from poultry and humans using multilocus sequence typing (MLST). Materials and methods: Salmonella spp. was isolated from clinical cases of gastroenteritis (n=110). Antibiotic susceptibility tests, followed by serotyping and MLST were conducted and S. Enteritidis was compared to those from laying hen farms and marketed eggs. Results: Ten isolates of Salmonella spp. were obtained from the stools of people with gastroenteritis. The prevalence of Salmonella spp. in human stools was 9.09%, and S. Enteritidis (n=4), S. Typhymurium (n=2), S. Newport (n=1), S. Uganda (n=1), S. Grupensis (n=1), and S. Braenderup (n=1) were the main serotypes. MLST indicated that a common S. Enteritidis sequence type (ST11) was present in all three sources and showed the same antibiotic resistance pattern. Conclusion: Salmonella Enteritidis ST11 constitutes a link between consumption and manipulation of contaminated eggs and human gastroenteritis in Ibagué. Additional studies would be required to establish if other Salmonella serovars isolated from raw chicken meat are also associated with human gastroenteritis.

Resumen Introducción. Salmonella Enteritidis es una de las mayores causas de salmonelosis en el mundo; los huevos contaminados y la carne de pollo cruda son sus principales fuentes de infección. En Ibagué, Colombia, se han identificado los principales serovares que circulan en granjas, superficies de huevos y canales de pollo, pero se desconoce si esos serovares son responsables de la gastroenteritis. Objetivo. Evaluar la relación genética entre los aislamientos de Salmonella Enteritidis de aves de corral y de humanos con la gastroenteritis mediante tipificación de multiloci de secuencias (Multilocus Sequence Typing, MLST). Materiales y métodos. Se aisló Salmonella spp. de casos clínicos de gastroenteritis (n=110). Se hizo la prueba de sensibilidad antibiótica, así como la serotipificación y la tipificación mediante MLST, y se comparó S. Enteritidis de humanos con la hallada en granjas de gallinas ponedoras y en huevo comercializado (n=6). Resultados. Se aislaron 10 cepas de Salmonella spp. a partir de heces de humanos con gastroenteritis. Se obtuvo una prevalencia de Salmonella spp. de 9,09%, y se identificaron los serotipos S. Enteritidis (n=4), S. Typhymurium (n=2), S. Newport (n=1), S. Grupensis (n=1), S. Uganda (n=1) y S. Braenderup presentes en pacientes con gastroenteritis. Mediante la MLST, se comprobó que un tipo de secuencia común (ST11) de S. Enteritidis estuvo presente en todas las tres fuentes y presentó el mismo patrón de resistencia antibiótica. Conclusión. Salmonella Enteritidis ST11 constituye un vínculo entre el consumo y la manipulación de huevos contaminados, y la gastroenteritis en humanos en Ibagué. Se requieren estudios complementarios para conocer si otros serovares de Salmonella aislados de carne de pollo cruda también se asocian con la gastroenteritis en humanos.

Bat Reservoirs for Rabies Virus and Epidemiology of Rabies in Colombia: a review / Murciélagos reservorios del virus de la Rabia y epidemiologia de la Rabia en Colombia: una revisión / Reservatórios de morcegos do vírus da raiva e epidemiologia da raiva na Colômbia: uma revisão

Abstract Rabies is a fatal zoonotic disease caused by a neurotropic RNA virus part of the family Rhabdoviridae. The disease is characterized by encephalitic inflammation and is responsible for a number of annual fatal deaths of people and animals in the world. Chiropters such as insectivorous, frugivorous and hematophagous bats are the major transmitters, reservoirs, and vectors of the rabies virus. In Colombia, a total of thirty-five cases of human rabies occurred between 2000 2014. Of the thirty-five cases twenty-two were transmitted by bats. The genetic variant V3 (hematophagous bats) were responsible for 24 human deaths, while the genetic variant V4, carried by insectivorous bats, caused three human deaths. The disease is mainly linked to infected cats that may have hunted infected bats and then transmitted the virus to humans. Diagnosis is usually made by detection of the virus from infected animals and techniques such as RT-PCR, which might be used to promote active surveillance in bat populations. Rabies is a preventable disease and vaccination of pets confers protective immunity, however, vaccination coverage of pets in Colombia is still limited. This review article collects epidemiological data of rabies virus genetic variants associated with chiropters species that have been reported to transmit the virus in the world and emphasizes on rabies cases reported in Colombia during the last decades.

Resumen La rabia es una enfermedad zoonóticas mortal causada por un virus ARN neurotrópico de la familia Rhabdoviridae. La enfermedad se caracteriza por encefalitis y es responsable de múltiples muertes anuales de personas y animales. Quirópteros insectívoros, frugívoros y hematófagos son los principales transmisores, reservorios y vectores del virus. En Colombia, un total de 35 casos de rabia humana fueron reportados entre 2000- 2014, veintidós de ellos fueron transmitidos por murciélagos. La variante genética V3 (murciélagos hematófagos) fue responsable de 24 muertes humanas, mientras que la variante genética V4 (murciélagos insectívoros) causó tres muertes humanas. La enfermedad es transmitida al humano principalmente por gatos infectados que pudieron haber cazado murciélagos infectados. El diagnóstico se realiza mediante la detección del virus en animales rabiosos y técnicas como RT-PCR podrían utilizarse para promover la vigilancia activa de las poblaciones de murciélagos. La rabia es una enfermedad prevenible y la vacunación en animales domésticos confiere inmunidad protectora, sin embargo, la cobertura de vacunación en animales domésticos en Colombia es aún limitada. Esta revisión recoge datos epidemiológicos de las variantes genéticas del virus en especies de quirópteros reportadas como transmisores del virus en el mundo y enfatiza en los casos de rabia reportados en Colombia durante las últimas décadas.

Resumo A raiva é uma enfermidade zoonótica fatal causada pelo vírus neurotrópico do ARN da família Rhabdoviridae. A enfermidade é conhecida por encefalite e é responsável das numerosas mortes anuais de animais e pessoas. Quirópteros e insetívoros, frugívoros e sanguessugas são os principais transmissores, reservatórios e vetores do vírus. Na Colômbia o Instituto Nacional de Saúde relatou um total de 35 casos de raiva humana entre 2000- 2014. Vinte dois deles foram transmitidos pelos morcegos. A variante genética V3 (morcegos hematófagos) foi responsável de 24 mortes humanas. Enquanto a variante genética V4 (morcegos insetívoros) provoco três mortes humanas. A enfermidade está ligada principalmente á os gatos infectados que poderiam ter caçado morcegos infectados e, em seguida, transmitida a os seres humanos. Diagnóstico e normalmente feito a través da detecção do vírus em animais raivosos e técnicas tais como RT- PCR poderiam se utilizar para promover a vigilância ativa das populações de morcegos. A raiva é uma enfermidade evitável em animais domésticos cuja vacinação confere imunidade protetora, no entanto, a cobertura de vacinação em animais de estimação na Colômbia ainda é limitada, precisando de mais cobertura. Este artigo de revisão recolha dados epidemiológicos e variantes genéticas do vírus, e a diversidade de espécies de morcego reportado como transmissores do vírus no mundo. O manuscrito também resume os principais casos de raiva reportados na Colômbia nas últimas décadas e enfatiza a necessidade de reforçar a vigilância ativa para o diagnóstico de raiva em morcegos em todo o país.

Prevalencia de anticuerpos anti-Leptospira spp. en personas con exposición laboral en el departamento del Tolima / Prevalence of anti-Leptospira spp. antibodies among people with occupational exposure in Tolima department / Prevalência de anticorpos anti-Leptospira spp. em pessoas com exposição laboral no Departamento do Tolima

Objetivo: estimar la prevalencia de anticuerpos IgM contra Leptospira spp., mediante el Ensayo de Inmunoabsorción Ligado a Enzimas (ELISA), en la población de riesgo laboral de 8 municipios del Tolima. Metodología: se obtuvieron muestras de sangre de 261 empleados, las cuales fueron analizadas mediante la técnica de elisa para la detección de anticuerpos IgM anti-Leptospira spp., seguido de MAT y serotipificación. Resultado : se estimó una seroprevalencia del 25,29%, con una seroreactividad mayor en trabajadores de plantas de beneficio animal (34,2%), recolección de residuos sólidos (27,1%) y trabajadores de acueducto y alcantarillado (14,8%). La actividad en plantas de beneficio animal se identificó como factor de riesgo de Leptospira spp. (OR=1,86). Los serovares identificados fueron L. Bratislava (16), Ballum (5), Tarassovi (3), Hebdomadis (2), Sejroe (2) y Icterhemorragiae (1). El municipio de Libano presentó el mayor porcentaje de positividad (36,96%), seguido de Espinal y Guamo con 28,57% cada uno. Discusión: La evaluación del sistema de vigilancia indicó deficiencia en recursos y debilidades de los profesionales de la salud al desconocer los procedimientos, investigación, diagnóstico y notificación de la enfermedad. Conclusión: la leptospirosis está presente en poblaciones de riesgo laboral en el Tolima y se hace necesario abordar esta problemática en la población de otros municipios y los animales transmisores de la enfermedad.

Objective: to estimate the prevalence of IgM antibodies against Leptospira spp. Using the enzyme-linked immunosorbent assay (elisa) in a population at occupational risk from 8 municipalities of the Tolima department, Colombia. Methodology: blood samples were collected from 261 employees and analyzed with the elisa technique to detect IgM and anti-Leptospira spp. antibodies. This was followed by mat and serotyping. Result: a seroprevalence of 25.29% was estimated, with higher seroreactivity for individuals working at slaughter plants (34.2%), collecting solid waste (27.1%) and those in contact with water and sewage waste (14.8%). Activity in slaughter plants was identified as a risk factor for Leptospira spp. (OR = 1.86). The serovars identified were L. Bratislava (16), Ballum (5), Tarassovi (3), Hebdomadis (2), Sejroe (2), and Icterhemorragiae (1). The municipality of Libano had the highest percentage of positivity (36.96%), followed by Espinal and Guamo with 28.57% each. Discussion: assessment of the current surveillance system for leptospirosis indicated deficient resources and health professionals who are lacking in terms of knowledge regarding appropriate procedures, research on, diagnosis and reporting mechanisms for the disease. Conclusions: leptospirosis is present in public workers with occupational hazard in Tolima. In addition, this issue should be approached while taking into account the population from other municipalities as well as the animals associated with its transmission

Objetivo: estimam a prevalência de anticorpos IgM contra Leptospira spp., por ensaio de ensaio de imunossorvente ligado a enzima (ELISA) na população de risco ocupacional de 8 municípios de Tolima. Metodologia: Coletaram-se amostras de sangue de 261 empregados, e analisaram-se com a técnica de ELISA para detectar anticorpos IgM anti-Leptospira spp., seguido de MAT e de serotipificação. Resultados : estimou-se uma seroprevalência de 25,29%, com seroatividade superior nos trabalhadores dos matadouros (34,2%), da recolecção de lixo sólido (27,1%), e nos trabalhadores dos esgotos (14,8%). A atividade nos matadouros foi identificada como fator de risco de Leptospira spp. (OR=1,86). Os serovares identificados foram L. Bratislava (16), Ballum K(5), Tarassovi K(3), Hebdomadis (2), Sejroe (2) e Icterhemorragiae (1). O município de Libano apresentou a percentagem mais alta de positividade (36,96%), seguido por Espinal e por Guamo, com 28,57 cada um. Discussão: a avaliação do sistema de vigilância revelou deficiência de recursos e fraquezas dos profissionais da saúde, porque desconhecem os procedimentos, a investigação, o diagnóstico e a notificação da doença. Conclusão: a leptospirosis está nas populações de risco laboral no Departamento do Tolima, o que faz necessário acometer este problema na população de outros municípios e nos animais transmissores da doença.

Campylobacter spp. in poultry products and its impact in public health / Campylobacter spp. en productos aviares y su impacto en salud pública / Campylobacter spp. em produtos de origem aviária e seu impacto na saúdepublica

Campylobacteriosis is a foodborne disease caused by species of Campylobacter and is a public health problem of worldwide distribution. The disease has an acute, self-limiting character, with symptoms such as watery to bloody diarrhea, fever, nausea and vomit, and it affects mainly children under 5 years, elderly and immunocompromised patients. The disease has also been associated with other complications such as arthritis, irritable bowel syndrome, Guillain-Barré or Miller-Fisher syndrome, among others. The main route of infection is through consumption of contaminated poultry meat or through direct contact with infected animals. The frequency of the disease increases continuously and around 190,566 cases of campylobacteriosis are reported annually in the whole world. However, in Colombia the diagnosis, isolation and molecular characterization of the pathogen are currently unknown. In this review, the characteristics, main sources of infection and reservoirs of Campylobacter are described, as well as the molecular techniques most frequently used for its diagnosis and characterization.

La campilobacteriosis causada por especies de Campylobacter es una enfermedad trasmitida por alimentos (ETA) y un problema de salud pública de distribución mundial. La enfermedad es de carácter agudo, autolimitante con síntomas como diarrea acuosa hasta sanguinolenta, fiebre, náuseas y vómito, que afecta principalmente a niños menores de 5 años, ancianos y pacientes inmunocomprometidos. La enfermedad también se ha asociado con otras complicaciones como artritis, síndrome de inflamación intestinal, el síndrome Guillain - Barré o el síndrome Miller - Fisher entre otros. La principal ruta de infección es a través del consumo de carne de pollo contaminada o a través de contacto directo con animales infectados. La frecuencia de la enfermedad incrementa en forma continua y alrededor de 190.566 casos de campilobacteriosis se reportan al año en todo el mundo. Sin embargo en Colombia el diagnóstico de la enfermedad, el aislamiento y la caracterización molecular del patógeno son actualmente desconocidos. En esta revisión se describen las características de la infección por Campylobacter, las principales fuentes de infección y reservorios, así como las técnicas moleculares empleadas con mayor frecuencia en su diagnóstico y caracterización.

A campilobacteriose causada por espécies de Campylobacter é uma doença transmitida por alimentos (ETA) e é um grande problema de saúde pública de presença mundial. A doença é de caráter agudo, auto limitante, com sintomas como diarreia aquosa até sanguinolenta, febre, náuseas e vomito, que afeta principalmente as crianças menores de 5 anos, idosos e pacientes imunocomprometidos. A doença também tem se associado com outras complicações como artrite, síndrome de inflamação intestinal, a síndrome Guillain-Barré ou síndrome Miller-Fisher entre outros. A principal rota de infecção é a traves do consumo de carne de frango contaminada ou a traves do contato direto com animais infetados. A frequência da doença está incrementando em forma continua e a cada ano reportam-se ao redor do mundo 190.566 casos de campilobacteriose. Porém, na Colômbia o diagnóstico da doença, o isolamento e a caracterização molecular do patógeno são atualmente desconhecidos. Nesta revisão descrevem-se as características da infecção por Campylobacter, as principais fontes de infecção e reservatórios, assim como as técnicas moleculares empregadas com maior frequência em seu diagnóstico e caracterização.

Constitutive plasmacytoid dendritic cell migration to the splenic white pulp is cooperatively regulated by CCR7- and CXCR4-mediated signaling.

Although the spleen plays an important role in host defense against infection, the mechanism underlying the migration of the innate immune cells, plasmacytoid dendritic cells (pDCs), into the spleen remains ill defined. In this article, we report that pDCs constitutively migrate into the splenic white pulp (WP) in a manner dependent on the chemokine receptors CCR7 and CXCR4. In CCR7-deficient mice and CCR7 ligand-deficient mice, compared with wild-type (WT) mice, substantially fewer pDCs were found in the periarteriolar lymphoid sheath of the splenic WP under steady-state conditions. In addition, the migration of adoptively transferred CCR7-deficient pDCs into the WP was significantly worse than that of WT pDCs, supporting the idea that pDC trafficking to the splenic WP requires CCR7 signaling. WT pDCs responded to a CCR7 ligand with modest chemotaxis and ICAM-1 binding in vitro, and priming with the CCR7 ligand enabled the pDCs to migrate efficiently toward low concentrations of CXCL12 in a CXCR4-dependent manner, raising the possibility that CCR7 signaling enhances CXCR4-mediated pDC migration. In agreement with this hypothesis, CCL21 and CXCL12 were colocalized on fibroblastic reticular cells in the T cell zone and in the marginal zone bridging channels, through which pDCs appeared to enter the WP. Furthermore, functional blockage of CCR7 and CXCR4 abrogated pDC trafficking into the WP. Collectively, these results strongly suggest that pDCs employ both CCR7 and CXCR4 as critical chemokine receptors to migrate into the WP under steady-state conditions.

SIRPα/CD172a regulates eosinophil homeostasis.

Eosinophils are abundant in the lamina propria of the small intestine, but they rarely show degranulation in situ under steady-state conditions. In this study, using two novel mAbs, we found that intestinal eosinophils constitutively expressed a high level of an inhibitory receptor signal regulatory protein α (SIRPα)/CD172a and a low, but significant, level of a tetraspanin CD63, whose upregulation is closely associated with degranulation. Cross-linking SIRPα/CD172a on the surface of wild-type eosinophils significantly inhibited the release of eosinophil peroxidase induced by the calcium ionophore A23187, whereas this cross-linking effect was not observed in eosinophils isolated from mice expressing a mutated SIRPα/CD172a that lacks most of its cytoplasmic domain (SIRPα Cyto(-/-)). The SIRPα Cyto(-/-) eosinophils showed reduced viability, increased CD63 expression, and increased eosinophil peroxidase release with or without A23187 stimulation in vitro. In addition, SIRPα Cyto(-/-) mice showed increased frequencies of Annexin V-binding eosinophils and free MBP(+)CD63(+) extracellular granules, as well as increased tissue remodeling in the small intestine under steady-state conditions. Mice deficient in CD47, which is a ligand for SIRPα/CD172a, recapitulated these phenomena. Moreover, during Th2-biased inflammation, increased eosinophil cell death and degranulation were obvious in a number of tissues, including the small intestine, in the SIRPα Cyto(-/-) mice compared with wild-type mice. Collectively, our results indicated that SIRPα/CD172a regulates eosinophil homeostasis, probably by interacting with CD47, with substantial effects on eosinophil survival. Thus, SIRPα/CD172a is a potential therapeutic target for eosinophil-associated diseases.