Respiratory and sweat gland ionocytes
Provided herein are methods and compositions for identifying ionocytes from respiratory epithelial cells, and uses of such cells for treatment of inflammatory lung disease. Also provided herein are methods and compositions for modulating respiratory tract epithelial cell proliferation, differentiation, maintenance, and/or function.
1. A method for increasing expression of CFTR in epithelial ionocytes, the method comprising delivering in vivo to a subject in need thereof one or more modulating agents comprising an adenovirus viral vector (AAV) comprising a polynucleotide sequence encoding FOXI1, wherein delivery of the polynucleotide sequence encoding FOXI1 increases the expression of FOXI1 and CFTR in the epithelial ionocytes.
2. The method of claim 1 , wherein the subject suffers from an inflammatory lung disease.
3. The method of claim 2 , wherein the inflammatory lung disease is asthma, bronchitis, cystic fibrosis, infection, emphysema, lung cancer, pulmonary hypertension, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, or α-1-anti-trypsin deficiency.
4. The method of claim 2 , wherein the inflammatory lung disease is cystic fibrosis.
5. The method of claim 1 , wherein the AAV is an AAV5 viral vector.
6. The method of claim 1 , wherein the viral vector is administered as an aerosol.
7. The method of claim 5 , wherein the vector comprises a deletion of base pairs 355 to 3325 to eliminate E1a and E1b functions, a deletion of base pairs 3325 to 4021 to eliminate protein IX function, and a deletion of base pairs 28592 to 30470 to eliminate E3 functions.
8. The method of claim 1 , wherein the polynucleotide sequence encoding FOXI1 comprises set forth in NCBI Reference Sequence NM_144769.