RESUMEN
Phenotypic definition of helper ILC1 and NK cells is problematic due to overlapping markers. Recently we showed the identification of cytotoxic ILC3s characterized by expression of CD94. Here we analyse CD127+ ILCs and NK cells in intestinal lamina propria from healthy donors and Crohn's disease patients and identify two populations of CD127+CD94+ ILCs, designated population A and B, that can be distinguished on the expression of CD117, CD18 and cytotoxic molecules. Population B expresses granulysin, a cytotoxic molecule linked to bacterial lysis and/or chemotaxis of monocytes. Granulysin protein is secreted by population B cells upon stimulation with IL-15. Activation of population B in the presence of TGF-ß strongly reduces the expression of cytotoxic effector molecules of population B. Strikingly, samples from individuals that suffer from active Crohn's disease display enhanced frequencies of granulysin-expressing effector CD127+CD94+ ILCs in comparison to controls. Thus this study identifies group 1 ILC populations which accumulate in inflamed intestinal tissue of Crohn's disease patients and may play a role in the pathology of the disease.
Asunto(s)
Antígenos de Diferenciación de Linfocitos T/metabolismo , Enfermedad de Crohn/inmunología , Enfermedad de Crohn/metabolismo , Subunidad alfa del Receptor de Interleucina-7/metabolismo , Linfocitos/metabolismo , Subfamília D de Receptores Similares a Lectina de las Células NK/metabolismo , Perforina/metabolismo , Antígenos de Diferenciación de Linfocitos T/genética , Células Cultivadas , Enfermedad de Crohn/genética , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Humanos , Inmunidad Innata/genética , Inmunidad Innata/fisiología , Inflamación/inmunología , Inflamación/metabolismo , Linfocitos/inmunología , Perforina/genética , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Innate lymphoid cells (ILC) represent a group of lymphocytes that lack specific antigen receptors and are relatively rare as compared to adaptive lymphocytes. ILCs play important roles in allergic and nonallergic inflammatory diseases due to their location at barrier surfaces within the airways, gut, and skin, and they respond to cytokines produced by activated cells in their local environment. Innate lymphoid cells contribute to the immune response by the release of cytokines and other mediators, forming a link between innate and adaptive immunity. In recent years, these cells have been extensively characterized and their role in animal models of disease has been investigated. Data to translate the relevance of ILCs in human pathology, and the potential role of ILCs in diagnosis, as biomarkers and/or as future treatment targets are also emerging. This review, produced by a task force of the Immunology Section of the European Academy of Allergy and Clinical Immunology (EAACI), encompassing clinicians and researchers, highlights the role of ILCs in human allergic and nonallergic diseases in the airways, gastrointestinal tract, and skin, with a focus on new insights into clinical implications, therapeutic options, and future research opportunities.
Asunto(s)
Hipersensibilidad/inmunología , Inmunidad Innata/inmunología , Inflamación/inmunología , Linfocitos/inmunología , Animales , HumanosRESUMEN
It is generally believed that inflammatory bowel diseases (IBD) are caused by an aberrant immune response to environmental triggers in genetically susceptible individuals. The exact contribution of the adaptive and innate immune system has not been elucidated. However, recent advances in treatments targeting key inflammatory mediators such as tumour necrosis factor highlight the crucial role of the innate immune system in IBD. Innate lymphoid cells (ILCs) have recently been identified to play an important role in immune mediated inflammatory diseases. In this review we recapitulate the current knowledge on ILCs in IBD.
