RESUMEN
The epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) has been associated with the promotion of type 2 inflammation and the induction of allergic disease. In humans TSLP is elevated in the lungs of asthma patients and in the lesional skin of individuals with atopic dermatitis, whereas mice lacking TSLP responses are refractory to models of Th2-driven allergic disease. Although several cell types, including dendritic cells, basophils, and CD4 T cells, have been shown to respond to TSLP, its role in macrophage differentiation has not been studied. Type 2 cytokines (i.e., IL-4 and IL-13) can drive the differentiation of macrophages into alternatively activated macrophages (aaMs, also referred to as M2 macrophages). This population of macrophages is associated with allergic inflammation. We therefore reasoned that TSLP/TSLPR signaling may be involved in the differentiation and activation of aaMs during allergic airway inflammation. In this study, we report that TSLP changes the quiescent phenotype of pulmonary macrophages toward an aaM phenotype during TSLP-induced airway inflammation. This differentiation of airway macrophages was IL-13-, but not IL-4-, dependent. Taken together, we demonstrate in this study that TSLP/TSLPR plays a significant role in the amplification of aaMΦ polarization and chemokine production, thereby contributing to allergic inflammation.
Asunto(s)
Asma/inmunología , Citocinas/farmacología , Activación de Macrófagos , Macrófagos/efectos de los fármacos , Animales , Asma/inducido químicamente , Asma/patología , Líquido del Lavado Bronquioalveolar/citología , Diferenciación Celular , Células Cultivadas/efectos de los fármacos , Quimiocinas/análisis , Citocinas/fisiología , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Femenino , Inmunoglobulinas/deficiencia , Inmunoglobulinas/genética , Inmunoglobulinas/fisiología , Interleucina-13/deficiencia , Interleucina-13/fisiología , Interleucina-4/deficiencia , Interleucina-4/fisiología , Pulmón/patología , Macrófagos/fisiología , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Ovalbúmina/toxicidad , Receptores de Citocinas/deficiencia , Receptores de Citocinas/genética , Receptores de Citocinas/fisiología , Factor de Transcripción STAT6/deficiencia , Factor de Transcripción STAT6/fisiología , Transducción de Señal , Organismos Libres de Patógenos Específicos , Linfopoyetina del Estroma TímicoRESUMEN
The cytokine thymic stromal lymphopoietin (TSLP) functions as a regulator of bone marrow B-cell development and a key initiator of allergic inflammation. In the current study, we show that mature B cells, derived from transgenic mice with systemically elevated levels of TSLP (K5-TSLP mice), exhibit markedly enhanced mitogenic responses in vitro and that this enhanced responsiveness leads to polyclonal B-cell activation and development of autoimmune hemolytic anemia in vivo. In contrast, B cells derived from K5-TSLP mice lacking CD4(+) T cells failed to show polyclonal activation. Furthermore, neither mature B-cell activation nor hemolytic anemia occurred in IL-4-deficient K5-TSLP mice. Consistent with these findings, activation of mature B cells occurred independently of B-cell intrinsic TSLP signals. Taken together, our results demonstrate that systemic alterations in TSLP, through induction of IL-4 from CD4(+) T cells and other cell types, functions as an important factor in peripheral B-cell homeostasis and promotion of humoral autoimmunity.
Asunto(s)
Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Citocinas/inmunología , Interleucina-4/inmunología , Activación de Linfocitos/inmunología , Anemia Hemolítica Autoinmune/inmunología , Animales , Autoinmunidad/inmunología , Separación Celular , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Ratones , Ratones Noqueados , Linfopoyetina del Estroma TímicoRESUMEN
INTRODUCTION/BACKGROUND: Leadership is defined as the ability to influence others to work towards common visions and goals. A key principle of the Australian Health Leadership Framework is that it applies to all leaders and potential leaders, who are at any place in the system. Hence, leadership is everyone's responsibility, including health profession students. In this short communication, we discuss the concept of leadership development in the undergraduate diagnostic radiography (DR) program through experiential learning. Examples from students' and academics' perspectives are presented, with the intention of providing a broad context to the range of opportunities that support development of leadership skills in DR students. DISCUSSION: Experience and experiential learning are fundamental and natural means of learning. Experiential learning has a positive effect on leadership because of its impact on personal, attitudinal, moral, social, and cognitive outcomes. Undergraduate DR students value opportunities to develop leadership skills during their university education. Four opportunities to develop and reflect on leadership skills are discussed. Two of the opportunities, clinical placements and honours programs, form part of the curricula, whilst others, such as mentoring and profession-specific social groups, are not. Through experience-based learning, students may benefit from transformational effects in their individual skills, which may ultimately benefit the organisation or community in which the individual participates. CONCLUSION: Commitment from clinical and academic educators to enable leadership development in DR students is essential. Through implementation of obligatory and optional experiential learning opportunities, it is anticipated that leadership skills will be cultivated in DR students, enabling students to exercise effective leadership in their current student roles and establish essential skills for their future professional roles.