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1.
Annu Rev Immunol ; 39: 557-581, 2021 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-33651964

RESUMEN

There is a growing interest in understanding tissue organization, homeostasis, and inflammation. However, despite an abundance of data, the organizing principles of tissue biology remain poorly defined. Here, we present a perspective on tissue organization based on the relationships between cell types and the functions that they perform. We provide a formal definition of tissue homeostasis as a collection of circuits that regulate specific variables within the tissue environment, and we describe how the functional organization of tissues allows for the maintenance of both tissue and systemic homeostasis. This leads to a natural definition of inflammation as a response to deviations from homeostasis that cannot be reversed by homeostatic mechanisms alone. We describe how inflammatory signals act on the same cellular functions involved in normal tissue organization and homeostasis in order to coordinate emergency responses to perturbations and ultimately return the system to a homeostatic state. Finally, we consider the hierarchy of homeostatic and inflammatory circuits and the implications for the development of inflammatory diseases.


Asunto(s)
Inflamación , Animales , Homeostasis , Humanos
2.
Cell ; 187(9): 2079-2094, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38670066

RESUMEN

Several conceptual pillars form the foundation of modern immunology, including the clonal selection theory, antigen receptor diversity, immune memory, and innate control of adaptive immunity. However, some immunological phenomena cannot be explained by the current framework. Thus, we still do not know how to design vaccines that would provide long-lasting protective immunity against certain pathogens, why autoimmune responses target some antigens and not others, or why the immune response to infection sometimes does more harm than good. Understanding some of these mysteries may require that we question existing assumptions to develop and test alternative explanations. Immunology is increasingly at a point when, once again, exploring new perspectives becomes a necessity.


Asunto(s)
Alergia e Inmunología , Humanos , Animales , Alergia e Inmunología/tendencias , Inmunidad Adaptativa , Inmunidad Innata , Memoria Inmunológica
3.
Annu Rev Cell Dev Biol ; 39: 67-89, 2023 10 16.
Artículo en Inglés | MEDLINE | ID: mdl-37607470

RESUMEN

Animal tissues are made up of multiple cell types that are increasingly well-characterized, yet our understanding of the core principles that govern tissue organization is still incomplete. This is in part because many observable tissue characteristics, such as cellular composition and spatial patterns, are emergent properties, and as such, they cannot be explained through the knowledge of individual cells alone. Here we propose a complex systems theory perspective to address this fundamental gap in our understanding of tissue biology. We introduce the concept of cell categories, which is based on cell relations rather than cell identity. Based on these notions we then discuss common principles of tissue modularity, introducing compositional, structural, and functional tissue modules. Cell diversity and cell relations provide a basis for a new perspective on the underlying principles of tissue organization in health and disease.


Asunto(s)
Biología , Animales
4.
Cell ; 184(6): 1440-1454, 2021 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-33450204

RESUMEN

Food is simultaneously a source of essential nutrients and a potential source of lethal toxins and pathogens. Consequently, multiple sensory mechanisms evolved to monitor the quality of food based on the presence and relative abundance of beneficial and harmful food substances. These include the olfactory, gustatory, and gut chemosensory systems. Here we argue that, in addition to these systems, allergic immunity plays a role in food quality control by mounting allergic defenses against food antigens associated with noxious substances. Exaggeration of these defenses can result in pathological food allergy.


Asunto(s)
Hipersensibilidad a los Alimentos/patología , Alimentos/efectos adversos , Alérgenos/inmunología , Hipersensibilidad a los Alimentos/inmunología , Humanos , Inmunidad , Modelos Biológicos , Control de Calidad
5.
Cell ; 180(5): 847-861.e15, 2020 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-32142678

RESUMEN

Early life environmental exposure, particularly during perinatal period, can have a life-long impact on organismal development and physiology. The biological rationale for this phenomenon is to promote physiological adaptations to the anticipated environment based on early life experience. However, perinatal exposure to adverse environments can also be associated with adult-onset disorders. Multiple environmental stressors induce glucocorticoids, which prompted us to investigate their role in developmental programming. Here, we report that perinatal glucocorticoid exposure had long-term consequences and resulted in diminished CD8 T cell response in adulthood and impaired control of tumor growth and bacterial infection. We found that perinatal glucocorticoid exposure resulted in persistent alteration of the hypothalamic-pituitary-adrenal (HPA) axis. Consequently, the level of the hormone in adults was significantly reduced, resulting in decreased CD8 T cell function. Our study thus demonstrates that perinatal stress can have long-term consequences on CD8 T cell immunity by altering HPA axis activity.


Asunto(s)
Infecciones Bacterianas/inmunología , Desarrollo Embrionario/inmunología , Glucocorticoides/efectos adversos , Efectos Tardíos de la Exposición Prenatal/genética , Animales , Infecciones Bacterianas/genética , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/patología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Proliferación Celular/efectos de los fármacos , Dexametasona/farmacología , Desarrollo Embrionario/genética , Femenino , Glucocorticoides/inmunología , Glucocorticoides/metabolismo , Humanos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/metabolismo , Interleucina-4/farmacología , Lipopolisacáridos/toxicidad , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/patología , Masculino , Neoplasias/inducido químicamente , Neoplasias/genética , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/inmunología , Efectos Tardíos de la Exposición Prenatal/patología , Receptores de Glucocorticoides/genética , Transducción de Señal/genética
6.
Cell ; 177(2): 223-224, 2019 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-30951664

RESUMEN

A relationship between thermoregulation, metabolism, and the host response to infections has long been appreciated. In this study, Ganeshan and colleagues discover that the immune system regulates body temperature as a strategy to regulate metabolic rate, which in turn promotes tolerance to inflammatory damage.


Asunto(s)
Regulación de la Temperatura Corporal , Inflamación , Temperatura Corporal , Humanos , Tolerancia Inmunológica
7.
Cell ; 178(5): 1231-1244.e11, 2019 08 22.
Artículo en Inglés | MEDLINE | ID: mdl-31402172

RESUMEN

Growth and differentiation factor 15 (GDF15) is an inflammation-associated hormone with poorly defined biology. Here, we investigated the role of GDF15 in bacterial and viral infections. We found that inflammation induced GDF15, and that GDF15 was necessary for surviving both bacterial and viral infections, as well as sepsis. The protective effects of GDF15 were largely independent of pathogen control or the magnitude of inflammatory response, suggesting a role in disease tolerance. Indeed, we found that GDF15 was required for hepatic sympathetic outflow and triglyceride metabolism. Failure to defend the lower limit of plasma triglyceride levels was associated with impaired cardiac function and maintenance of body temperature, effects that could be rescued by exogenous administration of lipids. Together, we show that GDF15 coordinates tolerance to inflammatory damage through regulation of triglyceride metabolism.


Asunto(s)
Factor 15 de Diferenciación de Crecimiento/metabolismo , Hígado/metabolismo , Sepsis/patología , Animales , Anticuerpos/farmacología , Modelos Animales de Enfermedad , Factor 15 de Diferenciación de Crecimiento/sangre , Factor 15 de Diferenciación de Crecimiento/genética , Factor 15 de Diferenciación de Crecimiento/inmunología , Corazón/efectos de los fármacos , Corazón/virología , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Lipopolisacáridos/toxicidad , Hígado/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Norepinefrina/metabolismo , Orthomyxoviridae/patogenicidad , Poli I-C/toxicidad , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/farmacología , Sepsis/sangre , Sepsis/mortalidad , Tasa de Supervivencia , Triglicéridos/sangre , Triglicéridos/metabolismo , Troponina I/sangre , Factor de Necrosis Tumoral alfa/sangre
8.
Cell ; 172(4): 744-757.e17, 2018 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-29398113

RESUMEN

Cell communication within tissues is mediated by multiple paracrine signals including growth factors, which control cell survival and proliferation. Cells and the growth factors they produce and receive constitute a circuit with specific properties that ensure homeostasis. Here, we used computational and experimental approaches to characterize the features of cell circuits based on growth factor exchange between macrophages and fibroblasts, two cell types found in most mammalian tissues. We found that the macrophage-fibroblast cell circuit is stable and robust to perturbations. Analytical screening of all possible two-cell circuit topologies revealed the circuit features sufficient for stability, including environmental constraint and negative-feedback regulation. Moreover, we found that cell-cell contact is essential for the stability of the macrophage-fibroblast circuit. These findings illustrate principles of cell circuit design and provide a quantitative perspective on cell interactions.


Asunto(s)
Comunicación Celular/fisiología , Proliferación Celular/fisiología , Fibroblastos/metabolismo , Macrófagos/metabolismo , Animales , Supervivencia Celular/fisiología , Femenino , Fibroblastos/citología , Macrófagos/citología , Masculino , Ratones , Ratones Transgénicos
9.
Immunity ; 56(4): 687-694, 2023 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-37044059

RESUMEN

Type 2 immunity defends against macro-parasites and can cause allergic diseases. Our understanding of the mechanisms governing the initiation of type 2 immunity is limited, whereas we know more about type 1 immune responses. Type 2 immunity can be triggered by a wide array of inducers that do not share common features and via diverse pathways and mechanisms. To address the complexity of the type 2 initiation pathways, we suggest a framework that conceptualizes different modes of induction of type 2 immunity. We discuss categories of type 2 inducers and their immunogenicity, types of tissue perturbations that are caused by these inducers, sensing strategies for the initiation of Th2 immune responses, and categorization of the signals that are produced in response to type 2 challenges. We describe tissue-specific examples of functional disruption that could lead to type 2 inflammation and propose that different sensing strategies that operate at the tissue level converge on the initiation of type 2 immune responses.


Asunto(s)
Hipersensibilidad , Inmunidad , Humanos , Inflamación , Células Th2
10.
Immunity ; 55(5): 895-911.e10, 2022 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-35483356

RESUMEN

Different effector arms of the immune system are optimized to protect from different classes of pathogens. In some cases, pathogens manipulate the host immune system to promote the wrong type of effector response-a phenomenon known as immune deviation. Typically, immune deviation helps pathogens to avoid destructive immune responses. Here, we report on a type of immune deviation whereby an opportunistic pathogen, Pseudomonas aeruginosa (P. aeruginosa), induces the type 2 immune response resulting in mucin production that is used as an energy source by the pathogen. Specifically, P. aeruginosa-secreted toxin, LasB, processed and activated epithelial amphiregulin to induce type 2 inflammation and mucin production. This "niche remodeling" by P. aeruginosa promoted colonization and, as a by-product, allergic sensitization. Our study thus reveals a type of bacterial immune deviation by increasing nutrient supply. It also uncovers a mechanism of allergic sensitization by a bacterial virulence factor.


Asunto(s)
Infecciones por Pseudomonas , Pseudomonas aeruginosa , Proteínas Bacterianas , Humanos , Inflamación , Mucinas
11.
Cell ; 165(3): 518-9, 2016 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-27104973

RESUMEN

Leukocyte recruitment is generally achieved by rapid migration of inflammatory cells out of circulation, through modified blood vessels, and into affected tissues. Now, Wang and Kubes show that macrophages can be rapidly recruited from body cavities to the liver, via a non-vascular route, where they help to coordinate tissue repair.


Asunto(s)
Leucocitos , Macrófagos , Humanos , Hígado/irrigación sanguínea
12.
Cell ; 165(2): 343-56, 2016 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-26997483

RESUMEN

Control of plasma glucose level is essential to organismal survival. Sustained inflammation has been implicated in control of glucose homeostasis in cases of infection, obesity, and type 2 diabetes; however, the precise role of inflammation in these complex disease states remains poorly understood. Here, we find that sustained inflammation results in elevated plasma glucose due to increased hepatic glucose production. We find that sustained inflammation suppresses CYP7A1, leading to accumulation of intermediate metabolites at the branch point of the mevalonate pathway. This results in prenylation of RHOC, which is concomitantly induced by inflammatory cytokines. Subsequent activation of RHO-associated protein kinase results in elevated plasma glucose. These findings uncover an unexpected mechanism by which sustained inflammation alters glucose homeostasis.


Asunto(s)
Vías Biosintéticas , Hepatitis/metabolismo , Hiperglucemia/metabolismo , Ácido Mevalónico/metabolismo , Animales , Glucemia/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Colesterol 7-alfa-Hidroxilasa/metabolismo , Ayuno/sangre , Lipopolisacáridos , Ratones , Ratones Obesos , Prenilación de Proteína , Transcripción Genética , Triglicéridos/sangre , Proteínas ras/metabolismo , Quinasas Asociadas a rho/metabolismo , Proteína rhoC de Unión a GTP
13.
Cell ; 166(6): 1512-1525.e12, 2016 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-27610573

RESUMEN

Acute infections are associated with a set of stereotypic behavioral responses, including anorexia, lethargy, and social withdrawal. Although these so-called sickness behaviors are the most common and familiar symptoms of infections, their roles in host defense are largely unknown. Here, we investigated the role of anorexia in models of bacterial and viral infections. We found that anorexia was protective while nutritional supplementation was detrimental in bacterial sepsis. Furthermore, glucose was necessary and sufficient for these effects. In contrast, nutritional supplementation protected against mortality from influenza infection and viral sepsis, whereas blocking glucose utilization was lethal. In both bacterial and viral models, these effects were largely independent of pathogen load and magnitude of inflammation. Instead, we identify opposing metabolic requirements tied to cellular stress adaptations critical for tolerance of differential inflammatory states. VIDEO ABSTRACT.


Asunto(s)
Manejo de la Enfermedad , Ayuno , Glucosa/metabolismo , Conducta de Enfermedad/fisiología , Gripe Humana/metabolismo , Listeriosis/metabolismo , Apoyo Nutricional/efectos adversos , Animales , Antimetabolitos/uso terapéutico , Células Cultivadas , Desoxiglucosa/uso terapéutico , Glucosa/administración & dosificación , Humanos , Inflamación , Gripe Humana/fisiopatología , Gripe Humana/terapia , Lipopolisacáridos , Listeriosis/mortalidad , Listeriosis/fisiopatología , Listeriosis/terapia , Masculino , Ratones , Ratones Endogámicos C57BL , Poli I-C , Sepsis/inducido químicamente , Sepsis/prevención & control , Factor de Transcripción CHOP/metabolismo
14.
Cell ; 160(5): 816-827, 2015 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-25723161

RESUMEN

While modernization has dramatically increased lifespan, it has also witnessed the increasing prevalence of diseases such as obesity, hypertension, and type 2 diabetes. Such chronic, acquired diseases result when normal physiologic control goes awry and may thus be viewed as failures of homeostasis. However, while nearly every process in human physiology relies on homeostatic mechanisms for stability, only some have demonstrated vulnerability to dysregulation. Additionally, chronic inflammation is a common accomplice of the diseases of homeostasis, yet the basis for this connection is not fully understood. Here we review the design of homeostatic systems and discuss universal features of control circuits that operate at the cellular, tissue, and organismal levels. We suggest a framework for classification of homeostatic signals that is based on different classes of homeostatic variables they report on. Finally, we discuss how adaptability of homeostatic systems with adjustable set points creates vulnerability to dysregulation and disease. This framework highlights the fundamental parallels between homeostatic and inflammatory control mechanisms and provides a new perspective on the physiological origin of inflammation.


Asunto(s)
Susceptibilidad a Enfermedades , Homeostasis , Inflamación/fisiopatología , Diabetes Mellitus/metabolismo , Humanos , Modelos Biológicos
15.
Cell ; 157(4): 832-44, 2014 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-24792964

RESUMEN

Tissue-resident macrophages are highly heterogeneous in terms of their functions and phenotypes as a consequence of adaptation to different tissue environments. Local tissue-derived signals are thought to control functional polarization of resident macrophages; however, the identity of these signals remains largely unknown. It is also unknown whether functional heterogeneity is a result of irreversible lineage-specific differentiation or a consequence of continuous but reversible induction of diverse functional programs. Here, we identified retinoic acid as a signal that induces tissue-specific localization and functional polarization of peritoneal macrophages through the reversible induction of transcription factor GATA6. We further found that GATA6 in macrophages regulates gut IgA production through peritoneal B-1 cells. These results provide insight into the regulation of tissue-resident macrophage functional specialization by tissue-derived signals.


Asunto(s)
Factor de Transcripción GATA6/metabolismo , Regulación de la Expresión Génica , Macrófagos Peritoneales/citología , Tretinoina/metabolismo , Animales , Inmunoglobulina A/genética , Macrófagos Peritoneales/metabolismo , Ratones , Ratones Endogámicos C57BL , Epiplón/citología
16.
Nature ; 620(7974): 643-650, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37437602

RESUMEN

In addition to its canonical function of protection from pathogens, the immune system can also alter behaviour1,2. The scope and mechanisms of behavioural modifications by the immune system are not yet well understood. Here, using mouse models of food allergy, we show that allergic sensitization drives antigen-specific avoidance behaviour. Allergen ingestion activates brain areas involved in the response to aversive stimuli, including the nucleus of tractus solitarius, parabrachial nucleus and central amygdala. Allergen avoidance requires immunoglobulin E (IgE) antibodies and mast cells but precedes the development of gut allergic inflammation. The ability of allergen-specific IgE and mast cells to promote avoidance requires cysteinyl leukotrienes and growth and differentiation factor 15. Finally, a comparison of C57BL/6 and BALB/c mouse strains revealed a strong effect of the genetic background on the avoidance behaviour. These findings thus point to antigen-specific behavioural modifications that probably evolved to promote niche selection to avoid unfavourable environments.


Asunto(s)
Alérgenos , Reacción de Prevención , Hipersensibilidad a los Alimentos , Animales , Ratones , Alérgenos/inmunología , Reacción de Prevención/fisiología , Núcleo Amigdalino Central/fisiología , Modelos Animales de Enfermedad , Hipersensibilidad a los Alimentos/genética , Hipersensibilidad a los Alimentos/inmunología , Inmunoglobulina E/inmunología , Intestinos/inmunología , Mastocitos/inmunología , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Núcleos Parabraquiales/fisiología , Núcleo Solitario/fisiología
17.
Nature ; 623(7985): 139-148, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37748514

RESUMEN

Post-acute infection syndromes may develop after acute viral disease1. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions2-4. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.


Asunto(s)
Anticuerpos Antivirales , Herpesvirus Humano 4 , Hidrocortisona , Linfocitos , Células Mieloides , Síndrome Post Agudo de COVID-19 , SARS-CoV-2 , Humanos , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Biomarcadores/sangre , Estudios Transversales , Herpesvirus Humano 4/inmunología , Hidrocortisona/sangre , Inmunofenotipificación , Linfocitos/inmunología , Aprendizaje Automático , Células Mieloides/inmunología , Síndrome Post Agudo de COVID-19/diagnóstico , Síndrome Post Agudo de COVID-19/inmunología , Síndrome Post Agudo de COVID-19/fisiopatología , Síndrome Post Agudo de COVID-19/virología , SARS-CoV-2/inmunología
18.
Nat Immunol ; 17(1): 9-17, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26681457

RESUMEN

Macrophages are essential components of mammalian tissues. Although historically known mainly for their function in host defense and the clearance of apoptotic cells, macrophages are now increasingly recognized as serving many roles in tissue development, homeostasis and repair. In addition, tissue-resident macrophages have many tissue-specific functional characteristics, which are a reflection of distinct gene-expression programs. Here we discuss the emerging views of macrophage biology from evolutionary, developmental and homeostatic perspectives.


Asunto(s)
Homeostasis/inmunología , Inmunidad Innata/inmunología , Macrófagos , Animales , Humanos
19.
Nat Immunol ; 16(4): 343-53, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25789684

RESUMEN

Microbial infections are recognized by the innate immune system both to elicit immediate defense and to generate long-lasting adaptive immunity. To detect and respond to vastly different groups of pathogens, the innate immune system uses several recognition systems that rely on sensing common structural and functional features associated with different classes of microorganisms. These recognition systems determine microbial location, viability, replication and pathogenicity. Detection of these features by recognition pathways of the innate immune system is translated into different classes of effector responses though specialized populations of dendritic cells. Multiple mechanisms for the induction of immune responses are variations on a common design principle wherein the cells that sense infections produce one set of cytokines to induce lymphocytes to produce another set of cytokines, which in turn activate effector responses. Here we discuss these emerging principles of innate control of adaptive immunity.


Asunto(s)
Inmunidad Adaptativa , Células Dendríticas/inmunología , Inmunidad Innata , Subgrupos Linfocitarios/inmunología , Animales , Bacterias/inmunología , Citocinas/genética , Citocinas/inmunología , Células Dendríticas/microbiología , Células Dendríticas/parasitología , Células Dendríticas/virología , Hongos/inmunología , Regulación de la Expresión Génica , Helmintos/inmunología , Humanos , Intestinos/inmunología , Intestinos/microbiología , Intestinos/parasitología , Intestinos/virología , Pulmón/inmunología , Pulmón/microbiología , Pulmón/parasitología , Pulmón/virología , Subgrupos Linfocitarios/microbiología , Subgrupos Linfocitarios/parasitología , Subgrupos Linfocitarios/virología , Receptores de Reconocimiento de Patrones/genética , Receptores de Reconocimiento de Patrones/inmunología , Piel/inmunología , Piel/microbiología , Piel/parasitología , Piel/virología , Virus/inmunología
20.
Proc Natl Acad Sci U S A ; 121(5): e2316446121, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38271336

RESUMEN

Eosinophils are well recognized as effector cells of type 2 immunity, yet they also accumulate in many tissues under homeostatic conditions. However, the processes that govern homeostatic eosinophil accumulation and tissue-specific adaptation, and their functional significance, remain poorly defined. Here, we investigated how eosinophils adapt to the small intestine (SI) microenvironment and the local signals that regulate this process. We observed that eosinophils gradually migrate along the crypt-villus axis, giving rise to a villus-resident subpopulation with a distinct transcriptional signature. Retinoic acid signaling was specifically required for maintenance of this subpopulation, while IL-5 was largely dispensable outside of its canonical role in eosinophil production. Surprisingly, we found that a high-protein diet suppressed the accumulation of villus-resident eosinophils. Purified amino acids were sufficient for this effect, which was a consequence of accelerated eosinophil turnover within the tissue microenvironment and was not due to altered development in the bone marrow. Our study provides insight into the process of eosinophil adaptation to the SI, highlighting its reliance on nutrient-derived signals.


Asunto(s)
Médula Ósea , Eosinófilos , Intestino Delgado , Linfocitos , Tretinoina
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