Can Controlling Endoplasmic Reticulum Dysfunction Treat Allergic Inflammation in Severe Asthma With Fungal Sensitization?.
10.4168/aair.2018.10.2.106
- Author:
Jae Seok JEONG
1
;
So Ri KIM
;
Yong Chul LEE
Author Information
1. Department of Internal Medicine, Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju, Korea. leeyc@jbnu.ac.kr
- Publication Type:Review
- Keywords:
Severe asthma;
fungi;
SAFS;
ER stress;
subcellular organelles;
innate immunity
- MeSH:
Aspergillosis, Allergic Bronchopulmonary;
Asthma*;
Biological Factors;
Endoplasmic Reticulum*;
Fungi;
Immunity, Innate;
Inflammation*;
Mitochondria;
Organelles;
Phenotype;
Pneumonia;
Precipitating Factors
- From:Allergy, Asthma & Immunology Research
2018;10(2):106-120
- CountryRepublic of Korea
- Language:English
-
Abstract:
Severe asthma is a heterogeneous disease entity to which diverse cellular components and pathogenetic mechanisms contribute. Current asthma therapies, including new biologic agents, are mainly targeting T helper type 2 cell-dominant inflammation, so that they are often unsatisfactory in the treatment of severe asthma. Respiratory fungal exposure has long been regarded as a precipitating factor for severe asthma phenotype. Moreover, as seen in clinical definitions of allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS), fungal allergy-associated severe asthma phenotype is increasingly thought to have distinct pathobiologic mechanisms requiring different therapeutic approaches other than conventional treatment. However, there are still many unanswered questions on the direct causality of fungal sensitization in inducing severe allergic inflammation in SAFS. Recently, growing evidence suggests that stress response from the largest organelle, endoplasmic reticulum (ER), is closely interconnected to diverse cellular immune/inflammatory platforms, thereby being implicated in severe allergic lung inflammation. Interestingly, a recent study on this issue has suggested that ER stress responses and several associated molecular platforms, including phosphoinositide 3-kinase-δ and mitochondria, may be crucial players in the development of severe allergic inflammation in the SAFS. Defining emerging roles of ER and associated cellular platforms in SAFS may offer promising therapeutic options in the near future.
