TH2-High Inflammation and Corticosteroid Response
I started out my quest trying to understand the relationship between Th2 or type 2 inflammation in severe asthma and its importance as well as its correlation to corticosteroids response. Firstly, I needed to begin, well at the beginning.
What is type 2 inflammation?
The answer to this question: Type 2 inflammation refers to an inflammatory pathway involving a subpopulation CD41 T cells known as Th2 cells that secrete IL-4, IL-5, and IL-13 and stimulate Type 2 immunity, which is characterized by high IgE antibody titers and eosinophilia.1
I personally find the illustration in Figure 1 of this journal article especially helpful when trying to understand these pathways. I know it is complex but if you digest it in bite-sized pieces, one at a time, you can get a sense of where you may align from you doctors or researchers. It may help you get a sense of what may be driving your inflammation.
Type 2 immune responses in the airway are mediated mainly by eosinophils, mast cells, basophils, Th2 cells, ILC2s, and IgE-producing B cells.2 Researchers believe that activation of airway epithethial cells, chemo-attraction of effector cells and chemo-attarction of the effector cells and remodelling of the airway epithelial and subeothial matrix. The combination of the inflammatory and patholologic changes in the airway is what is thought to predispose a person to exaggerated responses to inhaled trigger.3
Researchers are still untangling the complexity of immune response and untangling the connections between airway epithelium and airway smooth muscle and how these can help identify phenotypic manifestations. Essentially, what makes them a phentoype.4
To make things even more confusing is the change in the nomenclature to represent the finding that there is data that has identified rare innate cell subtype (ILC2) which is group 2 innate lymphoid cells had the ability to act on inflammation through the generation of substantial quantities of of type 2 cytokines.4
Now that you are still digesting the cellular stuff, how do you combat these cells and their associated inflammation? Type 2 inflammation is suppressed by steroids. Steroids suppress suppress the multiple inflammatory processes by reversing histone acetylation of activated inflammatory genes through binding of liganded glucocorticoid receptors (GR) to coactivators and recruitment of histone deacetylase-2 (HDAC2) to the activated transcription complex.5 Essentially, an attachment of the receptor to the gene that is being activated.
Steroids have a long list of bad things that they do at high doses. For example, local side effects and systemic ones such as cataracts, osteoporosis, adrenal suppression. These are most seen when steroids are taken at higher doses. It is also important to note that not everyone response to steroids in the same way.
The good news is that researchers are working on identifying more specific bio markers and developing targeted therapies for asthmatics with those biomarkers.
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