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Jehan Alladina, MD








Assistant in Medicine




J. Alladina1*, N.P. Smith1, K. Manakongtreecheep1, K. Slowikowski1, H.L. Keen2, T. Kooistra1, R.A. Rahimi1, F.L. Giacona1, A.D. Luster1, A.C. Villani1, J.L. Cho2 and B.D. Medoff1

A human model of asthma exacerbation identifies pathogenic airway immune circuits specific to asthma

My goal is to become an independent physician-scientist who elucidates mucosal pathways of homeostasis and inflammation in vivo to advance the understanding pulmonary inflammatory disease. To this end, I have pursued rigorous training in translational research and immunology to identify innate immune programs in the lung that sustain chronic inflammation in asthma. As a first-generation college graduate and women in medicine and science, I have had limited interactions with women role models along this path. I was thrilled to learn about this Symposium as an opportunity to build a community of women researchers both for mentorship and scientific collaboration.


We leveraged a translational model of asthma exacerbation in allergic asthmatics (AA) and allergic non-asthmatic controls (AC) to identify tissue-specific pathways driving asthma pathogenesis.


We performed single-cell RNA-sequencing of airway mucosal cells collected in vivo at homeostasis and after segmental allergen challenge (SAC). Logistic regression and LASSO modeling identified cellular and transcriptional programs associated with each group. CellphoneDB predicted receptor-ligand interactions specific to each group. Bronchoalveolar lavage (BAL) protein levels were quantified via multiplex assay.


Type-2 T helper cells (TH2) (OR 3.43, [1.87-6.29]), inflammatory type 2 dendritic cells (DC2) (OR 2.11, [1.23-3.61]) and CCR2hi monocyte-derived cells (MC) (OR 2.77, [1.29-5.92]) were enriched in AA after SAC, while macrophage-like MC that maintain airway homeostasis were enriched in AC. Lymphotoxin (LT) genes positively associated with DC2 enrichment in AA and negatively associated with macrophage-like MC in AC (P<0.01).LT-a levels increased after SAC in AA but not AC (147.3 vs. 18.2 pg/mL, P=0.04). TH2-DC2 interactions promoting DC maturation (e.g., LT signaling) and TH2 chemotaxis and polarization were asthma-specific (P<0.001).


We identified novel airway immune circuits that distinguish asthma from allergy. A feedforward circuit of DC maturation and TH2 activation via LT signaling may provide a novel target for disease remission in asthma.