Sex Differences in Adaptive Immunity in Chronic Lung Disease

Asthma, chronic obstructive pulmonary lung disease (COPD), pulmonary hypertension, and fibrotic lung diseases have increased airway inflammation and remodeling that are regulated by the host’s innate and adaptive immune responses. A sex bias is well-established in these diseases, as females have an increased prevalence of asthma, pulmonary hypertension, and sarcoidosis compared to males. However, males have an increased prevalence of COPD and interstitial pulmonary fibrosis (IPF) compared to females. Sex hormones are important in increasing or decreasing innate and adaptive immune responses by regulating immune cell proliferation, cytokine expression, and antibody production. In this chapter, we will discuss how sex hormones regulate adaptive immune mechanisms driving airway inflammation and/or pulmonary fibrosis using both human epidemiology data and mouse models. We will also discuss how estrogen signaling increased and androgen signaling decreased T and B cell proliferation and cytokine production in culture as well as discuss future directions for research. Overall, this chapter will provide insight into how sex hormones regulate adaptive immune responses important in the pathogenesis of asthma and fibrotic lung diseases.