Hypersensitivity pneumonitis onset and severity is regulated by CD103 dendritic cell expression

Abstract

BackgroundPulmonary dendritic cells drive lung responses to foreign antigens, including Saccharopolyspora rectivirgula, a causative agent of hypersensitivity pneumonitis. While the airway inflammatory mechanisms involved in hypersensitivity pneumonitis are well described, the mechanisms leading to the break in homeostasis and hypersensitivity pneumonitis onset are not well-described, and could involve CD103+ dendritic cells, which are found at baseline and during inflammatory responses in the lung. However, recent demonstration of the ability of CD103+ dendritic cells to induce inflammatory responses starkly contrasts with their classically described role as regulatory cells. These discrepancies may be attributable to the lack of current information on the importance of CD103 expression and modulation on these cells during inflammatory episodes.MethodsTo verify the importance of CD103 expression in the regulation of hypersensitivity pneumonitis, wild-type and Cd103-/- mice were exposed intranasally to S. rectivirgula and airway inflammation was quantified. Surface expression of CD103 in response to S. rectivirgula exposure was studied and cell transfers were used to determine the relative importance of CD103 expression on dendritic cells and T cells in regulating the inflammation in hypersensitivity pneumonitis.ResultsCd103-/- mice developed an exacerbated inflammatory response as early as 18h following S. rectivirgula exposure. CD103 expression on dendritic cells was downregulated quickly following S. rectivirgula exposure, and cell transfers demonstrated that CD103 expression on dendritic cells specifically (and not T cells) regulates the onset and severity of this response.ConclusionAll in all, we demonstrate that CD103 expression by dendritic cells, but not T cells, is crucial for homeostasis maintenance and the regulation of the TH17 airway inflammatory response in hypersensitivity pneumonitis.

Lipopolysaccharide impacts murine CD103+ DC differentiation, altering the lung DC population balance

“…In this line of thought, we have previously demonstrated that a single exposure to Saccharopolyspora rectivirgula extract decreases the proportion of lung CD103 + DCs [10], altering the DC balance and likely contributing to the initiation of this hypersensitivity response. However, the exact mechanisms underlying this phenomenon remain unknown.…”

“…CD103 + DC1s and CD11b + DC2s are the major two DC populations in the lung at steady state . As they are functionally different , their simultaneous presence and various complementary functions insure lung homeostasis maintenance by supporting the efficient pulmonary immune response to a variety of stimuli.…”

Exposure to the Gram-Negative Bacteria Pseudomonas aeruginosa Influences the Lung Dendritic Cell Population Signature by Interfering With CD103 Expression

“…These times were chosen since CD103 is still expressed on cDCs at that time following LPS exposure ( Brassard et al., 2019 ), and because the increase in total cells in response to P. aeruginosa is slower than following LPS administration (data not shown). Of note, although CD103 is also present on T cells, they do not play a role in the rapid innate immune response to these agents ( Andrew et al., 1996 ; Bernatchez et al., 2017 ). Following the i.n.…”

Disruption in the balance between apolipoprotein A‐I and mast cell chymase in chronic hypersensitivity pneumonitis

“…25 Acute immune responses against inhalation of causative antigens is also important for the pathogenesis of HP, including antigen presentation by dendritic cells and Th1/Th17 responses. 26,27 Taking together, the increase of apoA-I concentration in BALF may reflect an anti-inflammatory response locally against inhalation of causative antigens in HP, although the direct secretion of apoA-I by lung cells into BALF has not yet been demonstrated. 12 In contrast, the expression of apoA-I was significantly lower in BALF from patients with chronic HP compared with acute HP.…”

“…ApoA‐I can attenuate antigen presentation and T‐cell activation by the decrease of major histocompatibility complex class II proteins in ovalbumin allergic mice model 25 . Acute immune responses against inhalation of causative antigens is also important for the pathogenesis of HP, including antigen presentation by dendritic cells and Th1/Th17 responses 26,27 . Taking together, the increase of apoA‐I concentration in BALF may reflect an anti‐inflammatory response locally against inhalation of causative antigens in HP, although the direct secretion of apoA‐I by lung cells into BALF has not yet been demonstrated 12 .…”