CD6 is Highly Expressed in Fatal Asthma Patients and May Modulate Bronchomotor Tone

Rationale: Th2 and Th17 cells contribute to airway remodeling, facilitate mucus secretion and increase airway hyperresponsiveness. CD6, a T cell co-stimulatory receptor, interacts with CD166 (ALCAM) and CD318 to modulate activation. We examined whether severe asthma subjects have increased CD6+ cells, the lung inflammatory environment alters CD166 or CD318 expression, and CD6 exposure of airway smooth muscle (ASM) modulates bronchomotor tone. Methods: Lungs (asthma, non-asthma, n=4/group) were lavaged and lymphocytes examined for CD6 by flow cytometry. Tissue was stained for CD166, CD318, CD3, and CD6. ASM stimulated with carbachol (Cch) or CD6-beads was examined for phosphorylation of myosin light chain (pMLC), paxillin (pPax), or cofilin (pCof). ASM were co-cultured with T cells ± IL-33 with CD166 and CD318 expression assessed. Results: Flow analysis showed no difference in CD6+ lavage cells from asthma vs. non-asthma donors. Tissue sections had large differences in lymphocyte number and CD3+/CD6+ cells, with CD166 and CD318 expression on ciliated and basal cells. ALCAM, but not cd318, expression increased in asthma ASM. CD6-coated beads increased pCof and pPax, but not pMLC, to similar levels to Cch. ASM co-cultured with differentiated Th1 cells showed decreased CD166, but not CD318 expression. Co-stimulation with Th1 cells + IL-33 markedly decreased ASM CD166 and CD318 expression. Conclusions: We demonstrate that CD6+ lymphocytes are significantly increased in fatal asthma lung tissue. Furthermore, CD6+ lymphocytes may modulate bronchomotor tone through actin cytoskeletal rearrangements in HASM, and that the inflammatory environment may influence CD6-dependent changes in bronchomotor tone.