William O'Connor, Jr.
University of North Carolina at Chapel Hill
Postdoctoral - Yale University
In the gastrointestinal tract, immune sensing of luminal content influences resident microbial communities, and the microbiota in turn educate cells of the immune system. These events drive powerful immune and inflammatory processes locally and in distal organ systems. The level of coordination and extent of signal integration in determining inflammatory outcomes in the GI is remarkable. Signals derived from resident and infiltrating immune cells, stromal cells, and the commensal microbiota all contribute, and most of this signal integration remains poorly understood.
Our long-term goal is to understand how inflammation and mucosal healing are controlled. Improper immunoregulation at the mucosa is thought to drive a number of inflammatory disorders, including the inflammatory bowel diseases (IBDs), and may facilitate the progression to neoplasia.
Among the myriad of soluble factors controlling the initiating and resolving phases of inflammatory processes are cytokines, which participate in both pro-inflammatory signaling as well as in mucosal healing. Cytokines are generally pleotrophic and function in a microenvironment- and context-specific fashion. In the intestine, cytokines may be pro-inflammatory, anti-inflammatory, or 'inflammation-neutral'. Th17-associated cytokines are of particular interest, modulating immune cell recruitment, antimicrobial host defense, and tissue-protective processes. Cytokine function and integrated responses are a recurring theme in our research and are long-standing interests. We are currently investigating several novel mechanisms governing inflammation and mucosal healing in the GI tract.
- Cytokine crowdsourcing: Non-TH17 sources of TH17-associated cytokines.
Busman-Sahay K, Walrath TM, and O’Connor W Jr.
J Leukoc Biol. Review. Epub ahead of print: Dec 29, 2014
- Diverting T helper cell trafficking through increased plasticity attenuates autoimmune encephalomyelitis.
Califano D, Sweeney KJ, Le H, VanValkenburgh J, Yager E, O'Connor W Jr, Kennedy JS, Jones DM, and Avram D.
J Clin Invest. 2014 Jan 2;124(1):174-87
- IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine.
Huber S, Gagliani N, Zenewicz LA, Huber FJ, Bosurgi L, Hu B, Hedl M, Zhang W, O'Connor W, Murphy AJ, Valenzuela DM, Yancopoulos GD, Booth CJ, Cho JH, Ouyang W, Abraham C, and Flavell RA.
Nature. 2012 Nov 8;491(7423): 259-63
- Control of TH17 cells occurs in the Small Intestine
Esplugues E, Huber S, Gagliani N, Hauser AE, Town T, Wan YY, O'Connor W Jr, Rongvaux A, Van Rooijen N, Haberman AM, Iwakura Y, Kuchroo VK, Kolls JK, Bluestone JA, Herold KC, and Flavell RA.
Nature. 2011 Jul 17;475 (7357): 514-8.
- Memory/effector (CD45RB(lo)) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intestinal pathology.
Kamanaka M, Huber S, Zenewicz LA, Gagliani N, Rathinam C, O'Connor W Jr, Wan YY, Nakae S, Iwakura Y, Hao L, and Flavell RA.
J Exp Med. 2011 May 9;208(5):1027-40.
- Th17 cells express IL-10R? and are controlled by Tr1 and Foxp3+-Treg cells in an IL-10 dependent manner.
Huber S, Gagliani N, Esplugues E, O’Connor W Jr., Huber FJ, Chaudhry A, Kamanaka M, Kobajashi Y, Booth CJ, Rudensky AY, Battaglia M, and Flavell RA.
Immunity. 2011 Apr 22;34(4):554-65.
- The dual nature of TH17 cells: shifting the focus to function.
O’Connor W Jr., Zenewicz, LA, and Flavell, RA. Perspective.
Nat. Immunol. 2010 Jun;11(6):471-6. Epub 2010 May 18.
- A protective function for interleukin 17A in T cell-mediated intestinal inflammation. O'Connor W Jr., Kamanaka M, Booth CJ, Town T, Nakae S, Iwakura Y, Kolls JK,
and Flavell RA.
Nat. Immunol. 2009 Jun;10(6):603-9.
- Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants.
Eisenbarth SC, Colegio OR, O'Connor W, Sutterwala FS, and Flavell RA.
Nature. 2008 Jun 19;453(7198):1122-6.